Background Early in human immunodeficiency virus type 1 (HIV-1)infection there is a decline in viral replication that has beenattributed to host immunity, but the components of this response,particularly the ability of cytotoxic T lymphocytes to controlviral burden and influence the outcome of disease, are poorlyunderstood.
Methods We prospectively studied 33 patients with primary HIV-1infection for HIV-specific activated cytotoxic T lymphocytesand memory cytotoxic T lymphocytes and compared these lymphocyteresponses with changes in viral load and clinical status overthe subsequent 18 to 24 months.
Results Soon after infection, activated HIV-specific cytotoxicT lymphocytes, mediated primarily by CD8+ cells, were detectedin 17 of 23 patients (74 percent). Memory cytotoxic T lymphocyteswere found in 6 of 6 patients tested (100 percent) during thefirst three months of infection and in 17 of 21 patients (81percent) tested during the first six months. The frequenciesof memory cytotoxic T lymphocytes varied markedly over time,but overall they declined over the first 6 to 8 months and thenstabilized over the next 12 to 18 months. The patients withhigher frequencies of Env-specific memory cytotoxic T lymphocyteshad a median level of plasma HIV-1 RNA about one third thatof the patients with lower frequencies (median number of RNAcopies per milliliter, 22,000 vs. 62,000; P = 0.006). Patientswith low frequencies of Env-specific memory cytotoxic T lymphocytes(or none) in early infection had a more rapid decline to lessthan 300 CD4+ cells per cubic millimeter (P = 0.05).
Conclusions In early HIV-1 infection, the induction of memorycytotoxic T lymphocytes, particularly those specific for Env,helps control viral replication and is associated with slowerdeclines in CD4+ cell counts. Host cytolytic effector responsesappear to delay the progression of HIV-1 disease.
Source Information
From the Departments of Medicine (L.M., T. Schacker, T. Shea, L.C., M.J.M.) and Laboratory Medicine (L.C.), School of Medicine, and the Department of Biostatistics, School of Public Health (J.H.), University of Washington; and the Division of Clinical Research, Fred Hutchinson Cancer Research Center (L.C., M.J.M.) — all in Seattle.
Address reprint requests to Dr. McElrath at the Fred Hutchinson Cancer Research Center, Program in Infectious Diseases, M115, 1124 Columbia St., Seattle, WA 98104.
Huang, S., Dunkley-Thompson, J., Tang, Y., Macklin, E. A., Steel-Duncan, J., Singh-Minott, I., Ryland, E. G., Smikle, M., Walker, B. D., Christie, C. D. C., Feeney, M. E.
(2008). Deficiency of HIV-Gag-Specific T Cells in Early Childhood Correlates with Poor Viral Containment. J. Immunol.
181: 8103-8111
[Abstract][Full Text]
Schoenly, K. A., Weiner, D. B.
(2008). Human Immunodeficiency Virus Type 1 Vaccine Development: Recent Advances in the Cytotoxic T-Lymphocyte Platform "Spotty Business". J. Virol.
82: 3166-3180
[Full Text]
Joseph, A., Zheng, J. H., Follenzi, A., DiLorenzo, T., Sango, K., Hyman, J., Chen, K., Piechocka-Trocha, A., Brander, C., Hooijberg, E., Vignali, D. A., Walker, B. D., Goldstein, H.
(2008). Lentiviral Vectors Encoding Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Receptor Genes Efficiently Convert Peripheral Blood CD8 T Lymphocytes into Cytotoxic T Lymphocytes with Potent In Vitro and In Vivo HIV-1-Specific Inhibitory Activity. J. Virol.
82: 3078-3089
[Abstract][Full Text]
Sen, P., Charini, W. A., Subbramanian, R. A., Manuel, E. R., Kuroda, M. J., Autissier, P. A., Letvin, N. L.
(2008). Clonal Focusing of Epitope-Specific CD8+ T Lymphocytes in Rhesus Monkeys following Vaccination and Simian-Human Immunodeficiency Virus Challenge. J. Virol.
82: 805-816
[Abstract][Full Text]
Cao, J., McNevin, J., McSweyn, M., Liu, Y., Mullins, J. I., McElrath, M. J.
(2008). Novel Cytotoxic T-Lymphocyte Escape Mutation by a Three-Amino-Acid Insertion in the Human Immunodeficiency Virus Type 1 p6Pol and p6Gag Late Domain Associated with Drug Resistance. J. Virol.
82: 495-502
[Abstract][Full Text]
Karlsson, I., Malleret, B., Brochard, P., Delache, B., Calvo, J., Le Grand, R., Vaslin, B.
(2007). Dynamics of T-Cell Responses and Memory T Cells during Primary Simian Immunodeficiency Virus Infection in Cynomolgus Macaques. J. Virol.
81: 13456-13468
[Abstract][Full Text]
Peut, V., Kent, S. J.
(2007). Utility of Human Immunodeficiency Virus Type 1 Envelope as a T-Cell Immunogen. J. Virol.
81: 13125-13134
[Abstract][Full Text]
Buonaguro, L., Tornesello, M. L., Buonaguro, F. M.
(2007). Human Immunodeficiency Virus Type 1 Subtype Distribution in the Worldwide Epidemic: Pathogenetic and Therapeutic Implications. J. Virol.
81: 10209-10219
[Full Text]
Northfield, J. W., Loo, C. P., Barbour, J. D., Spotts, G., Hecht, F. M., Klenerman, P., Nixon, D. F., Michaelsson, J.
(2007). Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ TEMRA Cells in Early Infection Are Linked to Control of HIV-1 Viremia and Predict the Subsequent Viral Load Set Point. J. Virol.
81: 5759-5765
[Abstract][Full Text]
Hasegawa, A., Moriya, C., Liu, H., Charini, W. A., Vinet, H. C., Subbramanian, R. A., Sen, P., Letvin, N. L., Kuroda, M. J.
(2007). Analysis of TCR{alpha}beta Combinations used by Simian Immunodeficiency Virus-Specific CD8+ T Cells in Rhesus Monkeys: Implications for CTL Immunodominance. J. Immunol.
178: 3409-3417
[Abstract][Full Text]
McKinnon, L. R., Ball, T. B., Wachihi, C., McLaren, P. J., Waruk, J. L. M., Mao, X., Ramdahin, S., Anzala, A. O., Kamene, J., Luo, M., Fowke, K. R., Plummer, F. A.
(2007). Epitope Cross-Reactivity Frequently Differs between Central and Effector Memory HIV-Specific CD8+ T Cells. J. Immunol.
178: 3750-3756
[Abstract][Full Text]
Manuel, E. R., Charini, W. A., Sen, P., Peyerl, F. W., Kuroda, M. J., Schmitz, J. E., Autissier, P., Sheeter, D. A., Torbett, B. E., Letvin, N. L.
(2006). Contribution of T-Cell Receptor Repertoire Breadth to the Dominance of Epitope-Specific CD8+ T-Lymphocyte Responses. J. Virol.
80: 12032-12040
[Abstract][Full Text]
Liu, Y., McNevin, J., Cao, J., Zhao, H., Genowati, I., Wong, K., McLaughlin, S., McSweyn, M. D., Diem, K., Stevens, C. E., Maenza, J., He, H., Nickle, D. C., Shriner, D., Holte, S. E., Collier, A. C., Corey, L., McElrath, M. J., Mullins, J. I.
(2006). Selection on the Human Immunodeficiency Virus Type 1 Proteome following Primary Infection. J. Virol.
80: 9519-9529
[Abstract][Full Text]
Elrefaei, M., Barugahare, B., Ssali, F., Mugyenyi, P., Cao, H.
(2006). HIV-Specific IL-10-Positive CD8+ T Cells Are Increased in Advanced Disease and Are Associated with Decreased HIV-Specific Cytolysis. J. Immunol.
176: 1274-1280
[Abstract][Full Text]
Wewers, M. D., Lemeshow, S., Lehman, A., Clanton, T. L., Diaz, P. T.
(2005). Lung CD4 Lymphocytes Predict Survival in Asymptomatic HIV Infection. Chest
128: 2262-2267
[Abstract][Full Text]
Sheth, P. M., Danesh, A., Shahabi, K., Rebbapragada, A., Kovacs, C., Dimayuga, R., Halpenny, R., MacDonald, K. S., Mazzulli, T., Kelvin, D., Ostrowski, M., Kaul, R.
(2005). HIV-Specific CD8+ Lymphocytes in Semen Are Not Associated with Reduced HIV Shedding. J. Immunol.
175: 4789-4796
[Abstract][Full Text]
Lemckert, A. A. C., Sumida, S. M., Holterman, L., Vogels, R., Truitt, D. M., Lynch, D. M., Nanda, A., Ewald, B. A., Gorgone, D. A., Lifton, M. A., Goudsmit, J., Havenga, M. J. E., Barouch, D. H.
(2005). Immunogenicity of Heterologous Prime-Boost Regimens Involving Recombinant Adenovirus Serotype 11 (Ad11) and Ad35 Vaccine Vectors in the Presence of Anti-Ad5 Immunity. J. Virol.
79: 9694-9701
[Abstract][Full Text]
Barouch, D. H., Yang, Z.-y., Kong, W.-p., Korioth-Schmitz, B., Sumida, S. M., Truitt, D. M., Kishko, M. G., Arthur, J. C., Miura, A., Mascola, J. R., Letvin, N. L., Nabel, G. J.
(2005). A Human T-Cell Leukemia Virus Type 1 Regulatory Element Enhances the Immunogenicity of Human Immunodeficiency Virus Type 1 DNA Vaccines in Mice and Nonhuman Primates. J. Virol.
79: 8828-8834
[Abstract][Full Text]
Koibuchi, T., Allen, T. M., Lichterfeld, M., Mui, S. K., O'Sullivan, K. M., Trocha, A., Kalams, S. A., Johnson, R. P., Walker, B. D.
(2005). Limited Sequence Evolution within Persistently Targeted CD8 Epitopes in Chronic Human Immunodeficiency Virus Type 1 Infection. J. Virol.
79: 8171-8181
[Abstract][Full Text]
Monceaux, V., Viollet, L., Petit, F., Fang, R. H. T., Cumont, M.-C., Zaunders, J., Hurtrel, B., Estaquier, J.
(2005). CD8+ T Cell Dynamics during Primary Simian Immunodeficiency Virus Infection in Macaques: Relationship of Effector Cell Differentiation with the Extent of Viral Replication. J. Immunol.
174: 6898-6908
[Abstract][Full Text]
Someya, K., Cecilia, D., Ami, Y., Nakasone, T., Matsuo, K., Burda, S., Yamamoto, H., Yoshino, N., Kaizu, M., Ando, S., Okuda, K., Zolla-Pazner, S., Yamazaki, S., Yamamoto, N., Honda, M.
(2005). Vaccination of Rhesus Macaques with Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Env V3 Elicits Neutralizing Antibody-Mediated Protection against Simian-Human Immunodeficiency Virus with a Homologous but Not a Heterologous V3 Motif. J. Virol.
79: 1452-1462
[Abstract][Full Text]
Smith, M. Z., Dale, C. J., De Rose, R., Stratov, I., Fernandez, C. S., Brooks, A. G., Weinfurter, J., Krebs, K., Riek, C., Watkins, D. I., O'Connor, D. H., Kent, S. J.
(2005). Analysis of Pigtail Macaque Major Histocompatibility Complex Class I Molecules Presenting Immunodominant Simian Immunodeficiency Virus Epitopes. J. Virol.
79: 684-695
[Abstract][Full Text]
Zheng, N. N., Kiviat, N. B., Sow, P. S., Hawes, S. E., Wilson, A., Diallo-Agne, H., Critchlow, C. W., Gottlieb, G. S., Musey, L., McElrath, M. J.
(2004). Comparison of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses in HIV-1- and HIV-2-Infected Individuals in Senegal. J. Virol.
78: 13934-13942
[Abstract][Full Text]
Aandahl, E. M., Quigley, M. F., Moretto, W. J., Moll, M., Gonzalez, V. D., Sonnerborg, A., Lindback, S., Hecht, F. M., Deeks, S. G., Rosenberg, M. G., Nixon, D. F., Sandberg, J. K.
(2004). Expansion of CD7low and CD7negative CD8 T-cell effector subsets in HIV-1 infection: correlation with antigenic load and reversion by antiretroviral treatment. Blood
104: 3672-3678
[Abstract][Full Text]
Zhang, H., Fayad, R., Wang, X., Quinn, D., Qiao, L.
(2004). Human Immunodeficiency Virus Type 1 Gag-Specific Mucosal Immunity after Oral Immunization with Papillomavirus Pseudoviruses Encoding Gag. J. Virol.
78: 10249-10257
[Abstract][Full Text]
Someya, K., Xin, K.-Q., Matsuo, K., Okuda, K., Yamamoto, N., Honda, M.
(2004). A Consecutive Priming-Boosting Vaccination of Mice with Simian Immunodeficiency Virus (SIV) gag/pol DNA and Recombinant Vaccinia Virus Strain DIs Elicits Effective Anti-SIV Immunity. J. Virol.
78: 9842-9853
[Abstract][Full Text]
Davenport, M. P., Ribeiro, R. M., Perelson, A. S.
(2004). Kinetics of Virus-Specific CD8+ T Cells and the Control of Human Immunodeficiency Virus Infection. J. Virol.
78: 10096-10103
[Abstract][Full Text]
Norris, P. J., Moffett, H. F., Yang, O. O., Kaufmann, D. E., Clark, M. J., Addo, M. M., Rosenberg, E. S.
(2004). Beyond Help: Direct Effector Functions of Human Immunodeficiency Virus Type 1-Specific CD4+ T Cells. J. Virol.
78: 8844-8851
[Abstract][Full Text]
Xiao, Z., Batista, L., Dee, S., Halbur, P., Murtaugh, M. P.
(2004). The Level of Virus-Specific T-Cell and Macrophage Recruitment in Porcine Reproductive and Respiratory Syndrome Virus Infection in Pigs Is Independent of Virus Load. J. Virol.
78: 5923-5933
[Abstract][Full Text]
Hirsch, V. M., Santra, S., Goldstein, S., Plishka, R., Buckler-White, A., Seth, A., Ourmanov, I., Brown, C. R., Engle, R., Montefiori, D., Glowczwskie, J., Kunstman, K., Wolinsky, S., Letvin, N. L.
(2004). Immune Failure in the Absence of Profound CD4+ T-Lymphocyte Depletion in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques. J. Virol.
78: 275-284
[Abstract][Full Text]
Geels, M. J., Cornelissen, M., Schuitemaker, H., Anderson, K., Kwa, D., Maas, J., Dekker, J. T., Baan, E., Zorgdrager, F., van den Burg, R., van Beelen, M., Lukashov, V. V., Fu, T.-M., Paxton, W. A., van der Hoek, L., Dubey, S. A., Shiver, J. W., Goudsmit, J.
(2003). Identification of Sequential Viral Escape Mutants Associated with Altered T-Cell Responses in a Human Immunodeficiency Virus Type 1-Infected Individual. J. Virol.
77: 12430-12440
[Abstract][Full Text]
Benlhassan-Chahour, K., Penit, C., Dioszeghy, V., Vasseur, F., Janvier, G., Riviere, Y., Dereuddre-Bosquet, N., Dormont, D., Le Grand, R., Vaslin, B.
(2003). Kinetics of Lymphocyte Proliferation during Primary Immune Response in Macaques Infected with Pathogenic Simian Immunodeficiency Virus SIVmac251: Preliminary Report of the Effect of Early Antiviral Therapy. J. Virol.
77: 12479-12493
[Abstract][Full Text]
Kong, W.-P., Huang, Y., Yang, Z.-Y., Chakrabarti, B. K., Moodie, Z., Nabel, G. J.
(2003). Immunogenicity of Multiple Gene and Clade Human Immunodeficiency Virus Type 1 DNA Vaccines. J. Virol.
77: 12764-12772
[Abstract][Full Text]
Nayak, B. P., Sailaja, G., Jabbar, A. M.
(2003). Enhancement of gp120-Specific Immune Responses by Genetic Vaccination with the Human Immunodeficiency Virus Type 1 Envelope Gene Fused to the Gene Coding for Soluble CTLA4. J. Virol.
77: 10850-10861
[Abstract][Full Text]
Daftarian, P., Ali, S., Sharan, R., Lacey, S. F., La Rosa, C., Longmate, J., Buck, C., Siliciano, R. F., Diamond, D. J.
(2003). Immunization with Th-CTL Fusion Peptide and Cytosine-Phosphate-Guanine DNA in Transgenic HLA-A2 Mice Induces Recognition of HIV-Infected T Cells and Clears Vaccinia Virus Challenge. J. Immunol.
171: 4028-4039
[Abstract][Full Text]
Cao, J., McNevin, J., Malhotra, U., McElrath, M. J.
(2003). Evolution of CD8+ T Cell Immunity and Viral Escape Following Acute HIV-1 Infection. J. Immunol.
171: 3837-3846
[Abstract][Full Text]
Okazaki, T., Pendleton, C. D., Lemonnier, F., Berzofsky, J. A.
(2003). Epitope-Enhanced Conserved HIV-1 Peptide Protects HLA-A2-Transgenic Mice Against Virus Expressing HIV-1 Antigen. J. Immunol.
171: 2548-2555
[Abstract][Full Text]
Barouch, D. H., McKay, P. F., Sumida, S. M., Santra, S., Jackson, S. S., Gorgone, D. A., Lifton, M. A., Chakrabarti, B. K., Xu, L., Nabel, G. J., Letvin, N. L.
(2003). Plasmid Chemokines and Colony-Stimulating Factors Enhance the Immunogenicity of DNA Priming-Viral Vector Boosting Human Immunodeficiency Virus Type 1 Vaccines. J. Virol.
77: 8729-8735
[Abstract][Full Text]
Musey, L., Ding, Y., Elizaga, M., Ha, R., Celum, C., McElrath, M. J.
(2003). HIV-1 Vaccination Administered Intramuscularly Can Induce Both Systemic and Mucosal T Cell Immunity in HIV-1-Uninfected Individuals. J. Immunol.
171: 1094-1101
[Abstract][Full Text]
Barouch, D. H., Kunstman, J., Glowczwskie, J., Kunstman, K. J., Egan, M. A., Peyerl, F. W., Santra, S., Kuroda, M. J., Schmitz, J. E., Beaudry, K., Krivulka, G. R., Lifton, M. A., Gorgone, D. A., Wolinsky, S. M., Letvin, N. L.
(2003). Viral Escape from Dominant Simian Immunodeficiency Virus Epitope-Specific Cytotoxic T Lymphocytes in DNA-Vaccinated Rhesus Monkeys. J. Virol.
77: 7367-7375
[Abstract][Full Text]
Alter, G., Hatzakis, G., Tsoukas, C. M., Pelley, K., Rouleau, D., LeBlanc, R., Baril, J.-G., Dion, H., Lefebvre, E., Thomas, R., Cote, P., Lapointe, N., Routy, J.-P., Sekaly, R.-P., Conway, B., Bernard, N. F.
(2003). Longitudinal Assessment of Changes in HIV-Specific Effector Activity in HIV-Infected Patients Starting Highly Active Antiretroviral Therapy in Primary Infection. J. Immunol.
171: 477-488
[Abstract][Full Text]
Cao, J., McNevin, J., Holte, S., Fink, L., Corey, L., McElrath, M. J.
(2003). Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8+ T Cells in Primary HIV-1 Infection. J. Virol.
77: 6867-6878
[Abstract][Full Text]
Dehghani, H., Puffer, B. A., Doms, R. W., Hirsch, V. M.
(2003). Unique Pattern of Convergent Envelope Evolution in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques: Association with CD4-Independent Usage of CCR5. J. Virol.
77: 6405-6418
[Abstract][Full Text]
Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R., Ahmed, R.
(2003). Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment. J. Virol.
77: 4911-4927
[Abstract][Full Text]
Montefiori, D. C., Altfeld, M., Lee, P. K., Bilska, M., Zhou, J., Johnston, M. N., Gao, F., Walker, B. D., Rosenberg, E. S.
(2003). Viremia Control Despite Escape from a Rapid and Potent Autologous Neutralizing Antibody Response After Therapy Cessation in an HIV-1-Infected Individual. J. Immunol.
170: 3906-3914
[Abstract][Full Text]
Abel, K., Compton, L., Rourke, T., Montefiori, D., Lu, D., Rothaeusler, K., Fritts, L., Bost, K., Miller, C. J.
(2003). Simian-Human Immunodeficiency Virus SHIV89.6-Induced Protection against Intravaginal Challenge with Pathogenic SIVmac239 Is Independent of the Route of Immunization and Is Associated with a Combination of Cytotoxic T-Lymphocyte and Alpha Interferon Responses. J. Virol.
77: 3099-3118
[Abstract][Full Text]
Sailaja, G., Husain, S., Nayak, B. P., Jabbar, A. M.
(2003). Long-Term Maintenance of gp120-Specific Immune Responses by Genetic Vaccination with the HIV-1 Envelope Genes Linked to the Gene Encoding Flt-3 Ligand. J. Immunol.
170: 2496-2507
[Abstract][Full Text]
Novitsky, V., Gilbert, P., Peter, T., McLane, M. F., Gaolekwe, S., Rybak, N., Thior, I., Ndung'u, T., Marlink, R., Lee, T. H., Essex, M.
(2002). Association between Virus-Specific T-Cell Responses and Plasma Viral Load in Human Immunodeficiency Virus Type 1 Subtype C Infection. J. Virol.
77: 882-890
[Abstract][Full Text]
Willey, R. L., Byrum, R., Piatak, M., Kim, Y. B., Cho, M. W., Rossio, J. L. Jr., Bess, J. Jr., Igarashi, T., Endo, Y., Arthur, L. O., Lifson, J. D., Martin, M. A.
(2002). Control of Viremia and Prevention of Simian-Human Immunodeficiency Virus-Induced Disease in Rhesus Macaques Immunized with Recombinant Vaccinia Viruses plus Inactivated Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Particles. J. Virol.
77: 1163-1174
[Abstract][Full Text]
Musey, L., Ding, Y., Cao, J., Lee, J., Galloway, C., Yuen, A., Jerome, K. R., McElrath, M. J.
(2002). Ontogeny and Specificities of Mucosal and Blood Human Immunodeficiency Virus Type 1-Specific CD8+ Cytotoxic T Lymphocytes. J. Virol.
77: 291-300
[Abstract][Full Text]
Boaz, M. J., Waters, A., Murad, S., Easterbrook, P. J., Vyakarnam, A.
(2002). Presence of HIV-1 Gag-Specific IFN-{gamma}+IL-2+ and CD28+IL-2+ CD4 T Cell Responses Is Associated with Nonprogression in HIV-1 Infection. J. Immunol.
169: 6376-6385
[Abstract][Full Text]
Buseyne, F., Scott-Algara, D., Porrot, F., Corre, B., Bellal, N., Burgard, M., Rouzioux, C., Blanche, S., Riviere, Y.
(2002). Frequencies of Ex Vivo-Activated Human Immunodeficiency Virus Type 1-Specific Gamma-Interferon-Producing CD8+ T Cells in Infected Children Correlate Positively with Plasma Viral Load. J. Virol.
76: 12414-12422
[Abstract][Full Text]
Jin, X., Gao, X., Ramanathan, M. Jr., Deschenes, G. R., Nelson, G. W., O'Brien, S. J., Goedert, J. J., Ho, D. D., O'Brien, T. R., Carrington, M.
(2002). Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+-T-Cell Responses for Groups of HIV-1-Infected Individuals with Different HLA-B*35 Genotypes. J. Virol.
76: 12603-12610
[Abstract][Full Text]
Learn, G. H., Muthui, D., Brodie, S. J., Zhu, T., Diem, K., Mullins, J. I., Corey, L.
(2002). Virus Population Homogenization following Acute Human Immunodeficiency Virus Type 1 Infection. J. Virol.
76: 11953-11959
[Abstract][Full Text]
Onanga, R., Kornfeld, C., Pandrea, I., Estaquier, J., Souquiere, S., Rouquet, P., Mavoungou, V. P., Bourry, O., M'Boup, S., Barre-Sinoussi, F., Simon, F., Apetrei, C., Roques, P., Muller-Trutwin, M. C.
(2002). High Levels of Viral Replication Contrast with Only Transient Changes in CD4+ and CD8+ Cell Numbers during the Early Phase of Experimental Infection with Simian Immunodeficiency Virus SIVmnd-1 in Mandrillus sphinx. J. Virol.
76: 10256-10263
[Abstract][Full Text]
Yusim, K., Kesmir, C., Gaschen, B., Addo, M. M., Altfeld, M., Brunak, S., Chigaev, A., Detours, V., Korber, B. T.
(2002). Clustering Patterns of Cytotoxic T-Lymphocyte Epitopes in Human Immunodeficiency Virus Type 1 (HIV-1) Proteins Reveal Imprints of Immune Evasion on HIV-1 Global Variation. J. Virol.
76: 8757-8768
[Abstract][Full Text]
Haglund, K., Leiner, I., Kerksiek, K., Buonocore, L., Pamer, E., Rose, J. K.
(2002). Robust Recall and Long-Term Memory T-Cell Responses Induced by Prime-Boost Regimens with Heterologous Live Viral Vectors Expressing Human Immunodeficiency Virus Type 1 Gag and Env Proteins. J. Virol.
76: 7506-7517
[Abstract][Full Text]
Marsac, D., Loirat, D., Petit, C., Schwartz, O., Michel, M.-L.
(2002). Enhanced Presentation of Major Histocompatibility Complex Class I-Restricted Human Immunodeficiency Virus Type 1 (HIV-1) Gag-Specific Epitopes after DNA Immunization with Vectors Coding for Vesicular Stomatitis Virus Glycoprotein- Pseudotyped HIV-1 Gag Particles. J. Virol.
76: 7544-7553
[Abstract][Full Text]
Santra, S., Barouch, D. H., Kuroda, M. J., Schmitz, J. E., Krivulka, G. R., Beaudry, K., Lord, C. I., Lifton, M. A., Wyatt, L. S., Moss, B., Hirsch, V. M., Letvin, N. L.
(2002). Prior Vaccination Increases the Epitopic Breadth of the Cytotoxic T-Lymphocyte Response That Evolves in Rhesus Monkeys following a Simian-Human Immunodeficiency Virus Infection. J. Virol.
76: 6376-6381
[Abstract][Full Text]
Chakrabarti, B. K., Kong, W.-p., Wu, B.-y., Yang, Z.-Y., Friborg, J., Ling, X., King, S. R., Montefiori, D. C., Nabel, G. J.
(2002). Modifications of the Human Immunodeficiency Virus Envelope Glycoprotein Enhance Immunogenicity for Genetic Immunization. J. Virol.
76: 5357-5368
[Abstract][Full Text]
Schmitz, J. L., Denny, T. N., Garcia, A., Lathey, J. L.
(2002). Comparison of Human Immunodeficiency Virus Antigens as Stimulants for Lymphocyte Proliferation Assays. CVI
9: 525-529
[Abstract][Full Text]
Kostense, S., Vandenberghe, K., Joling, J., Van Baarle, D., Nanlohy, N., Manting, E., Miedema, F.
(2002). Persistent numbers of tetramer+ CD8+ T cells, but loss of interferon-gamma + HIV-specific T cells during progression to AIDS. Blood
99: 2505-2511
[Abstract][Full Text]
Edwards, B. H., Bansal, A., Sabbaj, S., Bakari, J., Mulligan, M. J., Goepfert, P. A.
(2002). Magnitude of Functional CD8+ T-Cell Responses to the Gag Protein of Human Immunodeficiency Virus Type 1 Correlates Inversely with Viral Load in Plasma. J. Virol.
76: 2298-2305
[Abstract][Full Text]
Haglund, K., Leiner, I., Kerksiek, K., Buonocore, L., Pamer, E., Rose, J. K.
(2002). High-Level Primary CD8+ T-Cell Response to Human Immunodeficiency Virus Type 1 Gag and Env Generated by Vaccination with Recombinant Vesicular Stomatitis Viruses. J. Virol.
76: 2730-2738
[Abstract][Full Text]
Santra, S., Schmitz, J. E., Kuroda, M. J., Lifton, M. A., Nickerson, C. E., Lord, C. I., Pal, R., Franchini, G., Letvin, N. L.
(2002). Recombinant Canarypox Vaccine-Elicited CTL Specific for Dominant and Subdominant Simian Immunodeficiency Virus Epitopes in Rhesus Monkeys. J. Immunol.
168: 1847-1853
[Abstract][Full Text]
Betts, M. R., Ambrozak, D. R., Douek, D. C., Bonhoeffer, S., Brenchley, J. M., Casazza, J. P., Koup, R. A., Picker, L. J.
(2001). Analysis of Total Human Immunodeficiency Virus (HIV)-Specific CD4+ and CD8+ T-Cell Responses: Relationship to Viral Load in Untreated HIV Infection. J. Virol.
75: 11983-11991
[Abstract][Full Text]
McGettigan, J. P., Sarma, S., Orenstein, J. M., Pomerantz, R. J., Schnell, M. J.
(2001). Expression and Immunogenicity of Human Immunodeficiency Virus Type 1 Gag Expressed by a Replication-Competent Rhabdovirus-Based Vaccine Vector. J. Virol.
75: 8724-8732
[Abstract][Full Text]
Hansasuta, P., Rowland-Jones, S. L
(2001). HIV-1 transmission and acute HIV-1 infection. Br Med Bull
58: 109-127
[Abstract][Full Text]
Forthal, D. N., Landucci, G., Daar, E. S.
(2001). Antibody from Patients with Acute Human Immunodeficiency Virus (HIV) Infection Inhibits Primary Strains of HIV Type 1 in the Presence of Natural-Killer Effector Cells. J. Virol.
75: 6953-6961
[Abstract][Full Text]
Horner, A. A., Datta, S. K., Takabayashi, K., Belyakov, I. M., Hayashi, T., Cinman, N., Nguyen, M.-D., Van Uden, J. H., Berzofsky, J. A., Richman, D. D., Raz, E.
(2001). Immunostimulatory DNA-Based Vaccines Elicit Multifaceted Immune Responses Against HIV at Systemic and Mucosal Sites. J. Immunol.
167: 1584-1591
[Abstract][Full Text]
Kamin-Lewis, R., Abdelwahab, S. F., Trang, C., Baker, A., DeVico, A. L., Gallo, R. C., Lewis, G. K.
(2001). Perforin-low memory CD8+ cells are the predominant T cells in normal humans that synthesize the beta -chemokine macrophage inflammatory protein-1beta. Proc. Natl. Acad. Sci. USA
10.1073/pnas.161298998v1
[Abstract][Full Text]
Barouch, D. H., Santra, S., Kuroda, M. J., Schmitz, J. E., Plishka, R., Buckler-White, A., Gaitan, A. E., Zin, R., Nam, J.-H., Wyatt, L. S., Lifton, M. A., Nickerson, C. E., Moss, B., Montefiori, D. C., Hirsch, V. M., Letvin, N. L.
(2001). Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination. J. Virol.
75: 5151-5158
[Abstract][Full Text]
Hosmalin, A., Samri, A., Dumaurier, M.-J., Dudoit, Y., Oksenhendler, E., Karmochkine, M., Autran, B., Wain-Hobson, S., Cheynier, R.
(2001). HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients. Blood
97: 2695-2701
[Abstract][Full Text]
Xiong, Y., Luscher, M. A., Altman, J. D., Hulsey, M., Robinson, H. L., Ostrowski, M., Barber, B. H., MacDonald, K. S.
(2001). Simian Immunodeficiency Virus (SIV) Infection of a Rhesus Macaque Induces SIV-Specific CD8+ T Cells with a Defect in Effector Function That Is Reversible on Extended Interleukin-2 Incubation. J. Virol.
75: 3028-3033
[Abstract][Full Text]
Engelmayer, J., Larsson, M., Lee, A., Lee, M., Cox, W. I., Steinman, R. M., Bhardwaj, N.
(2001). Mature Dendritic Cells Infected with Canarypox Virus Elicit Strong Anti-Human Immunodeficiency Virus CD8+ and CD4+ T-Cell Responses from Chronically Infected Individuals. J. Virol.
75: 2142-2153
[Abstract][Full Text]
Barouch, D. H., Craiu, A., Santra, S., Egan, M. A., Schmitz, J. E., Kuroda, M. J., Fu, T.-M., Nam, J.-H., Wyatt, L. S., Lifton, M. A., Krivulka, G. R., Nickerson, C. E., Lord, C. I., Moss, B., Lewis, M. G., Hirsch, V. M., Shiver, J. W., Letvin, N. L.
(2001). Elicitation of High-Frequency Cytotoxic T-Lymphocyte Responses against both Dominant and Subdominant Simian-Human Immunodeficiency Virus Epitopes by DNA Vaccination of Rhesus Monkeys. J. Virol.
75: 2462-2467
[Abstract][Full Text]
Hladik, F., Bender, S., Akridge, R. E., Hu, Y., Galloway, C., Francis, D., McElrath, M. J.
(2001). Recombinant HIV-1 Glycoprotein 120 Induces Distinct Types of Delayed Hypersensitivity in Persons With or Without Pre-Existing Immunologic Memory. J. Immunol.
166: 3580-3588
[Abstract][Full Text]
Fu, T.-M., Freed, D. C., Trigona, W. L., Guan, L., Zhu, L., Long, R., Persaud, N. V., Manson, K., Dubey, S., Shiver, J. W.
(2001). Evaluation of Cytotoxic T-Lymphocyte Responses in Human and Nonhuman Primate Subjects Infected with Human Immunodeficiency Virus Type 1 or Simian/Human Immunodeficiency Virus. J. Virol.
75: 73-82
[Abstract][Full Text]
Ikuta, K., Suzuki, S., Horikoshi, H., Mukai, T., Luftig, R. B.
(2000). Positive and Negative Aspects of the Human Immunodeficiency Virus Protease: Development of Inhibitors versus Its Role in AIDS Pathogenesis. Microbiol. Mol. Biol. Rev.
64: 725-745
[Abstract][Full Text]
Goepfert, P. A., Bansal, A., Edwards, B. H., Ritter, G. D. Jr., Tellez, I., McPherson, S. A., Sabbaj, S., Mulligan, M. J.
(2000). A Significant Number of Human Immunodeficiency Virus Epitope-Specific Cytotoxic T Lymphocytes Detected by Tetramer Binding Do Not Produce Gamma Interferon. J. Virol.
74: 10249-10255
[Abstract][Full Text]
Barouch, D. H., Santra, S., Schmitz, J. E., Kuroda, M. J., Fu, T.-M., Wagner, W., Bilska, M., Craiu, A., Zheng, X. X., Krivulka, G. R., Beaudry, K., Lifton, M. A., Nickerson, C. E., Trigona, W. L., Punt, K., Freed, D. C., Guan, L., Dubey, S., Casimiro, D., Simon, A., Davies, M.-E., Chastain, M., Strom, T. B., Gelman, R. S., Montefiori, D. C., Lewis, M. G., Emini, E. A., Shiver, J. W., Letvin, N. L.
(2000). Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination. Science
290: 486-492
[Abstract][Full Text]
Goldstein, S., Brown, C. R., Dehghani, H., Lifson, J. D., Hirsch, V. M.
(2000). Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4+ T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication. J. Virol.
74: 9388-9395
[Abstract][Full Text]
Cooper, L. J. N., Kalos, M., Lewinsohn, D. A., Riddell, S. R., Greenberg, P. D.
(2000). Transfer of Specificity for Human Immunodeficiency Virus Type 1 into Primary Human T Lymphocytes by Introduction of T-Cell Receptor Genes. J. Virol.
74: 8207-8212
[Abstract][Full Text]
Dela Cruz, C. S., Tan, R., Rowland-Jones, S. L., Barber, B. H.
(2000). Creating HIV-1 reverse transcriptase cytotoxic T lymphocyte target structures by HLA-A2 heavy chain modifications. Int Immunol
12: 1293-1302
[Abstract][Full Text]
Kuroda, M. J., Schmitz, J. E., Seth, A., Veazey, R. S., Nickerson, C. E., Lifton, M. A., Dailey, P. J., Forman, M. A., Racz, P., Tenner-Racz, K., Letvin, N. L.
(2000). Simian immunodeficiency virus-specific cytotoxic T lymphocytes and cell-associated viral RNA levels in distinct lymphoid compartments of SIVmac-infected rhesus monkeys. Blood
96: 1474-1479
[Abstract][Full Text]
Mitsuyasu, R. T., Anton, P. A., Deeks, S. G., Scadden, D. T., Connick, E., Downs, M. T., Bakker, A., Roberts, M. R., June, C. H., Jalali, S., Lin, A. A., Pennathur-Das, R., Hege, K. M.
(2000). Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4+ and CD8+ T cells in human immunodeficiency virus-infected subjects. Blood
96: 785-793
[Abstract][Full Text]
Qiu, J.-T., Liu, B., Tian, C., Pavlakis, G. N., Yu, X.-F.
(2000). Enhancement of Primary and Secondary Cellular Immune Responses against Human Immunodeficiency Virus Type 1 Gag by Using DNA Expression Vectors That Target Gag Antigen to the Secretory Pathway. J. Virol.
74: 5997-6005
[Abstract][Full Text]
Rinaldo, C. R. Jr., Huang, X.-L., Fan, Z., Margolick, J. B., Borowski, L., Hoji, A., Kalinyak, C., McMahon, D. K., Riddler, S. A., Hildebrand, W. H., Day, R. B., Mellors, J. W.
(2000). Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+ T-Lymphocyte Reactivity during Combination Antiretroviral Therapy in HIV-1-Infected Patients with Advanced Immunodeficiency. J. Virol.
74: 4127-4138
[Abstract][Full Text]
Oxenius, A., Price, D. A., Easterbrook, P. J., O'Callaghan, C. A., Kelleher, A. D., Whelan, J. A., Sontag, G., Sewell, A. K., Phillips, R. E.
(2000). Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc. Natl. Acad. Sci. USA
97: 3382-3387
[Abstract][Full Text]
Seth, A., Ourmanov, I., Schmitz, J. E., Kuroda, M. J., Lifton, M. A., Nickerson, C. E., Wyatt, L., Carroll, M., Moss, B., Venzon, D., Letvin, N. L., Hirsch, V. M.
(2000). Immunization with a Modified Vaccinia Virus Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol Primes for an Anamnestic Gag-Specific Cytotoxic T-Lymphocyte Response and Is Associated with Reduction of Viremia after SIV Challenge. J. Virol.
74: 2502-2509
[Abstract][Full Text]
Soudeyns, H., Campi, G., Rizzardi, G. P., Lenge, C., Demarest, J. F., Tambussi, G., Lazzarin, A., Kaufmann, D., Casorati, G., Corey, L., Pantaleo, G.
(2000). Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor beta chain repertoire and reduces the level of T-cell oligoclonality. Blood
95: 1743-1751
[Abstract][Full Text]
Spiegel, H. M. L., Ogg, G. S., DeFalcon, E., Sheehy, M. E., Monard, S., Haslett, P. A. J., Gillespie, G., Donahoe, S. M., Pollack, H., Borkowsky, W., McMichael, A. J., Nixon, D. F.
(2000). Human Immunodeficiency Virus Type 1- and Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Persist at High Frequency for Prolonged Periods in the Absence of Circulating Peripheral CD4+ T Cells. J. Virol.
74: 1018-1022
[Abstract][Full Text]
Qiu, J.-T., Song, R., Dettenhofer, M., Tian, C., August, T., Felber, B. K., Pavlakis, G. N., Yu, X.-F.
(1999). Evaluation of Novel Human Immunodeficiency Virus Type 1 Gag DNA Vaccines for Protein Expression in Mammalian Cells and Induction of Immune Responses. J. Virol.
73: 9145-9152
[Abstract][Full Text]
Ogg, G. S., Kostense, S., Klein, M. R., Jurriaans, S., Hamann, D., McMichael, A. J., Miedema, F.
(1999). Longitudinal Phenotypic Analysis of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes: Correlation with Disease Progression. J. Virol.
73: 9153-9160
[Abstract][Full Text]
Furchner, M., Erickson, A. L., Allen, T., Watkins, D. I., Sette, A., Johnson, P. R., Walker, C. M.
(1999). The Simian Immunodeficiency Virus Envelope Glycoprotein Contains Two Epitopes Presented by the Mamu-A*01 Class I Molecule. J. Virol.
73: 8035-8039
[Abstract][Full Text]
Moyer, T. P., Temesgen, Z., Enger, R., Estes, L., Charlson, J., Oliver, L., Wright, A.
(1999). Drug Monitoring of Antiretroviral Therapy for HIV-1 Infection: Method Validation and Results of a Pilot Study. Clin. Chem.
45: 1465-1476
[Abstract][Full Text]
Greenberg, P. D., Riddell, S. R.
(1999). Deficient Cellular Immunity--Finding and Fixing the Defects. Science
285: 546-551
[Abstract][Full Text]
M. McKinney, D., Lewinsohn, D. A., Riddell, S. R., Greenberg, P. D., Mosier, D. E.
(1999). The Antiviral Activity of HIV-Specific CD8+ CTL Clones Is Limited by Elimination Due to Encounter with HIV-Infected Targets. J. Immunol.
163: 861-867
[Abstract][Full Text]
Egan, M. A., Kuroda, M. J., Voss, G., Schmitz, J. E., Charini, W. A., Lord, C. I., Forman, M. A., Letvin, N. L.
(1999). Use of Major Histocompatibility Complex Class I/Peptide/beta 2M Tetramers To Quantitate CD8+ Cytotoxic T Lymphocytes Specific for Dominant and Nondominant Viral Epitopes in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys. J. Virol.
73: 5466-5472
[Abstract][Full Text]
Kolowos, W., Schmitt, M., Herrman, M., Harrer, E., Low, P., Kalden, J. R., Harrer, T.
(1999). Biased TCR Repertoire in HIV-1-Infected Patients Due to Clonal Expansion of HIV-1-Reverse Transcriptase-Specific CTL Clones. J. Immunol.
162: 7525-7533
[Abstract][Full Text]
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