In a study designed to determine whether cytotoxic T lymphocytes contribute to immunity against influenza virus infection, we inoculated 63 volunteers intranasally with live unattenuated influenza A/Munich/1/79 virus. Over the next seven days clinical observations were made, and the amount of virus shed was measured. The protective effects of preinfection serum antibody and of cytotoxic T-cell immunity against influenza A virus were assessed for each participant. All subjects with demonstrable T-cell responses cleared virus effectively. This response was observed in volunteers in all age groups, including those born after 1956, who did not have specific antibody and hence had probably not been exposed to this subtype of influenza A virus before. Cytotoxic T cells show cross-reactivity in their recognition of the different subtypes of influenza A virus, in contrast to the antibody response that is specific for each virus subtype. We conclude that cytotoxic T cells play a part in recovery from influenza virus infection.
This article has been cited by other articles:
Forrest, B. D., Pride, M. W., Dunning, A. J., Capeding, M. R. Z., Chotpitayasunondh, T., Tam, J. S., Rappaport, R., Eldridge, J. H., Gruber, W. C.
(2008). Correlation of Cellular Immune Responses with Protection against Culture-Confirmed Influenza Virus in Young Children. CVI
15: 1042-1053
[Abstract][Full Text]
Kreijtz, J. H. C. M., de Mutsert, G., van Baalen, C. A., Fouchier, R. A. M., Osterhaus, A. D. M. E., Rimmelzwaan, G. F.
(2008). Cross-Recognition of Avian H5N1 Influenza Virus by Human Cytotoxic T-Lymphocyte Populations Directed to Human Influenza A Virus. J. Virol.
82: 5161-5166
[Abstract][Full Text]
Zheng, B., Zhang, Y., He, H., Marinova, E., Switzer, K., Wansley, D., Mbawuike, I., Han, S.
(2007). Rectification of Age-Associated Deficiency in Cytotoxic T Cell Response to Influenza A Virus by Immunization with Immune Complexes. J. Immunol.
179: 6153-6159
[Abstract][Full Text]
Richter, M., Ray, S. J., Chapman, T. J., Austin, S. J., Rebhahn, J., Mosmann, T. R., Gardner, H., Kotelianski, V., deFougerolles, A. R., Topham, D. J.
(2007). Collagen Distribution and Expression of Collagen-Binding {alpha}1beta1 (VLA-1) and {alpha}2beta1 (VLA-2) Integrins on CD4 and CD8 T Cells during Influenza Infection. J. Immunol.
178: 4506-4516
[Abstract][Full Text]
Draghi, M., Pashine, A., Sanjanwala, B., Gendzekhadze, K., Cantoni, C., Cosman, D., Moretta, A., Valiante, N. M., Parham, P.
(2007). NKp46 and NKG2D Recognition of Infected Dendritic Cells Is Necessary for NK Cell Activation in the Human Response to Influenza Infection. J. Immunol.
178: 2688-2698
[Abstract][Full Text]
He, X.-S., Holmes, T. H., Zhang, C., Mahmood, K., Kemble, G. W., Lewis, D. B., Dekker, C. L., Greenberg, H. B., Arvin, A. M.
(2006). Cellular Immune Responses in Children and Adults Receiving Inactivated or Live Attenuated Influenza Vaccines. J. Virol.
80: 11756-11766
[Abstract][Full Text]
Ferko, B., Kittel, C., Romanova, J., Sereinig, S., Katinger, H., Egorov, A.
(2006). Live Attenuated Influenza Virus Expressing Human Interleukin-2 Reveals Increased Immunogenic Potential in Young and Aged Hosts. J. Virol.
80: 11621-11627
[Abstract][Full Text]
Masopust, D., Ha, S.-J., Vezys, V., Ahmed, R.
(2006). Stimulation History Dictates Memory CD8 T Cell Phenotype: Implications for Prime-Boost Vaccination. J. Immunol.
177: 831-839
[Abstract][Full Text]
Boon, A. C. M., de Mutsert, G., Fouchier, R. A. M., Osterhaus, A. D. M. E., Rimmelzwaan, G. F.
(2006). The Hypervariable Immunodominant NP418-426 Epitope from the Influenza A Virus Nucleoprotein Is Recognized by Cytotoxic T Lymphocytes with High Functional Avidity.. J. Virol.
80: 6024-6032
[Abstract][Full Text]
Kuiken, T., Holmes, E. C., McCauley, J., Rimmelzwaan, G. F., Williams, C. S., Grenfell, B. T.
(2006). Host species barriers to influenza virus infections.. Science
312: 394-397
[Abstract][Full Text]
Perreau, M., Kremer, E. J.
(2005). Frequency, Proliferation, and Activation of Human Memory T Cells Induced by a Nonhuman Adenovirus. J. Virol.
79: 14595-14605
[Abstract][Full Text]
Flynn, J. N., Pistello, M., Isola, P., Zaccaro, L., Del Santo, B., Ricci, E., Matteucci, D., Bendinelli, M.
(2005). Adoptive Immunotherapy of Feline Immunodeficiency Virus with Autologous Ex Vivo-Stimulated Lymphoid Cells Modulates Virus and T-Cell Subsets in Blood. CVI
12: 736-745
[Abstract][Full Text]
Rimmelzwaan, G. F., Berkhoff, E. G. M., Nieuwkoop, N. J., Smith, D. J., Fouchier, R. A. M., Osterhaus, A. D. M. E.
(2005). Full restoration of viral fitness by multiple compensatory co-mutations in the nucleoprotein of influenza A virus cytotoxic T-lymphocyte escape mutants. J. Gen. Virol.
86: 1801-1805
[Abstract][Full Text]
Cooper, C. L., Davis, H., Cameron, D.W.
(2004). Influenza Vaccination with 1/10th the Full Dose. NEJM
351: 2339-2340
[Full Text]
Rimmelzwaan, G. F., Berkhoff, E. G. M., Nieuwkoop, N. J., Fouchier, R. A. M., Osterhaus, A. D. M. E.
(2004). Functional Compensation of a Detrimental Amino Acid Substitution in a Cytotoxic-T-Lymphocyte Epitope of Influenza A Viruses by Comutations. J. Virol.
78: 8946-8949
[Abstract][Full Text]
Berkhoff, E. G. M., Boon, A. C. M., Nieuwkoop, N. J., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., Rimmelzwaan, G. F.
(2004). A Mutation in the HLA-B*2705-Restricted NP383-391 Epitope Affects the Human Influenza A Virus-Specific Cytotoxic T-Lymphocyte Response In Vitro. J. Virol.
78: 5216-5222
[Abstract][Full Text]
Betts, M. R., Price, D. A., Brenchley, J. M., Lore, K., Guenaga, F. J., Smed-Sorensen, A., Ambrozak, D. R., Migueles, S. A., Connors, M., Roederer, M., Douek, D. C., Koup, R. A.
(2004). The Functional Profile of Primary Human Antiviral CD8+ T Cell Effector Activity Is Dictated by Cognate Peptide Concentration. J. Immunol.
172: 6407-6417
[Abstract][Full Text]
Boon, A. C. M., de Mutsert, G., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., Rimmelzwaan, G. F.
(2004). Preferential HLA Usage in the Influenza Virus-Specific CTL Response. J. Immunol.
172: 4435-4443
[Abstract][Full Text]
Boon, A. C. M., de Mutsert, G., van Baarle, D., Smith, D. J., Lapedes, A. S., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., Rimmelzwaan, G. F.
(2004). Recognition of Homo- and Heterosubtypic Variants of Influenza A Viruses by Human CD8+ T Lymphocytes. J. Immunol.
172: 2453-2460
[Abstract][Full Text]
Flynn, J. N., Dunham, S. P., Watson, V., Jarrett, O.
(2002). Longitudinal Analysis of Feline Leukemia Virus-Specific Cytotoxic T Lymphocytes: Correlation with Recovery from Infection. J. Virol.
76: 2306-2315
[Abstract][Full Text]
Boon, A. C. M., de Mutsert, G., Graus, Y. M. F., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., Rimmelzwaan, G. F.
(2002). The Magnitude and Specificity of Influenza A Virus-Specific Cytotoxic T-Lymphocyte Responses in Humans Is Related to HLA-A and -B Phenotype. J. Virol.
76: 582-590
[Abstract][Full Text]
Koralnik, I. J., Du Pasquier, R. A., Kuroda, M. J., Schmitz, J. E., Dang, X., Zheng, Y., Lifton, M., Letvin, N. L.
(2002). Association of Prolonged Survival in HLA-A2+ Progressive Multifocal Leukoencephalopathy Patients with a CTL Response Specific for a Commonly Recognized JC Virus Epitope. J. Immunol.
168: 499-504
[Abstract][Full Text]
Goronzy, J. J., Fulbright, J. W., Crowson, C. S., Poland, G. A., O'Fallon, W. M., Weyand, C. M.
(2001). Value of Immunological Markers in Predicting Responsiveness to Influenza Vaccination in Elderly Individuals. J. Virol.
75: 12182-12187
[Abstract][Full Text]
Vignuzzi, M., Gerbaud, S., van der Werf, S., Escriou, N.
(2001). Naked RNA immunization with replicons derived from poliovirus and Semliki Forest virus genomes for the generation of a cytotoxic T cell response against the influenza A virus nucleoprotein. J. Gen. Virol.
82: 1737-1747
[Abstract][Full Text]
Couch, R. B.
(2000). Influenza: Prospects for Control. ANN INTERN MED
133: 992-998
[Abstract][Full Text]
Haller, A. A., Miller, T., Mitiku, M., Coelingh, K.
(2000). Expression of the Surface Glycoproteins of Human Parainfluenza Virus Type 3 by Bovine Parainfluenza Virus Type 3, a Novel Attenuated Virus Vaccine Vector. J. Virol.
74: 11626-11635
[Abstract][Full Text]
Goulder, P. J. R., Lechner, F., Klenerman, P., McIntosh, K., Walker, B. D.
(2000). Characterization of a Novel Respiratory Syncytial Virus-Specific Human Cytotoxic T-Lymphocyte Epitope. J. Virol.
74: 7694-7697
[Abstract][Full Text]
Cerwenka, A., Morgan, T. M., Dutton, R. W.
(1999). Naive, Effector, and Memory CD8 T Cells in Protection Against Pulmonary Influenza Virus Infection: Homing Properties Rather Than Initial Frequencies Are Crucial. J. Immunol.
163: 5535-5543
[Abstract][Full Text]
Ishioka, G. Y., Fikes, J., Hermanson, G., Livingston, B., Crimi, C., Qin, M., France del Guercio, M., Oseroff, C., Dahlberg, C., Alexander, J., Chesnut, R. W., Sette, A.
(1999). Utilization of MHC Class I Transgenic Mice for Development of Minigene DNA Vaccines Encoding Multiple HLA-Restricted CTL Epitopes. J. Immunol.
162: 3915-3925
[Abstract][Full Text]
Jin, X., Bauer, D. E., Tuttleton, S. E., Lewin, S., Gettie, A., Blanchard, J., Irwin, C. E., Safrit, J. T., Mittler, J., Weinberger, L., Kostrikis, L. G., Zhang, L., Perelson, A. S., Ho, D. D.
(1999). Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus-infected Macaques. J. Exp. Med.
189: 991-998
[Abstract][Full Text]
Balla-Jhagjhoorsingh, S. S., Koopman, G., Mooij, P., Haaksma, T. G. M., Teeuwsen, V. J. P., Bontrop, R. E., Heeney, J. L.
(1999). Conserved CTL Epitopes Shared Between HIV-Infected Human Long-Term Survivors and Chimpanzees. J. Immunol.
162: 2308-2314
[Abstract][Full Text]
Jameson, J., Cruz, J., Ennis, F. A.
(1998). Human Cytotoxic T-Lymphocyte Repertoire to Influenza A Viruses. J. Virol.
72: 8682-8689
[Abstract][Full Text]
Nguyen, H. H., Boyaka, P. N., Moldoveanu, Z., Novak, M. J., Kiyono, H., McGhee, J. R., Mestecky, J.
(1998). Influenza Virus-Infected Epithelial Cells Present Viral Antigens to Antigen-Specific CD8+ Cytotoxic T Lymphocytes. J. Virol.
72: 4534-4536
[Abstract][Full Text]
Wong, D. K. H., Dudley, D. D., Afdhal, N. H., Dienstag, J., Rice, C. M., Wang, L., Houghton, M., Walker, B. D., Koziel, M. J.
(1998). Liver-Derived CTL in Hepatitis C Virus Infection: Breadth and Specificity of Responses in a Cohort of Persons with Chronic Infection. J. Immunol.
160: 1479-1488
[Abstract][Full Text]
Matano, T., Shibata, R., Siemon, C., Connors, M., Lane, H. C., Martin, M. A.
(1998). Administration of an Anti-CD8 Monoclonal Antibody Interferes with the Clearance of Chimeric Simian/Human Immunodeficiency Virus during Primary Infections of Rhesus Macaques. J. Virol.
72: 164-169
[Abstract][Full Text]
Goletz, T. J., Klimpel, K. R., Arora, N., Leppla, S. H., Keith, J. M., Berzofsky, J. A.
(1997). Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein. Proc. Natl. Acad. Sci. USA
94: 12059-12064
[Abstract][Full Text]
Lalvani, A., Brookes, R., Hambleton, S., Britton, W. J., Hill, A. V.S., McMichael, A. J.
(1997). Rapid Effector Function in CD8+ Memory T Cells. J. Exp. Med.
186: 859-865
[Abstract][Full Text]
Ferrari, G., Berend, C., Ottinger, J., Dodge, R., Bartlett, J., Toso, J., Moody, D., Tartaglia, J., Cox, W. I., Paoletti, E., Weinhold, K.J.
(1997). Replication-Defective Canarypox (ALVAC) Vectors Effectively Activate Anti-Human Immunodeficiency Virus-1 Cytotoxic T Lymphocytes Present in Infected Patients: Implications for Antigen-Specific Immunotherapy. Blood
90: 2406-2416
[Abstract][Full Text]
Ferrari, G., Humphrey, W., McElrath, M. J., Excler, J.-L., Duliege, A.-M., Clements, M. L., Corey, L. C., Bolognesi, D. P., Weinhold, K. J.
(1997). Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers. Proc. Natl. Acad. Sci. USA
94: 1396-1401
[Abstract][Full Text]
Ulmer, J., Donnelly, J., Parker, S., Rhodes, G., Felgner, P., Dwarki, V., Gromkowski, S., Deck, R., DeWitt, C., Friedman, A, et, al.
(1993). Heterologous protection against influenza by injection of DNA encoding a viral protein. Science
259: 1745-1749
[Abstract]
Walker, B., Flexner, C, Paradis, T., Fuller, T., Hirsch, M., Schooley, R., Moss, B
(1988). HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals. Science
240: 64-66
[Abstract]