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Previous Volume 333:1038-1044 October 19, 1995 Number 16 Next

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ABSTRACT

Background Cytomegalovirus (CMV) disease in immunocompromised patients correlates with a deficiency of CD8+ cytotoxic T lymphocytes specific for CMV. We evaluated the safety and immunologic effects of immunotherapy with clones of these lymphocytes in recipients of allogeneic bone marrow transplants.

Methods Clones of CD8+ cytotoxic T cells specific for CMV proteins were isolated from the blood of bone marrow donors. Fourteen patients each received four intravenous infusions of these clones from their donors beginning 30 to 40 days after marrow transplantation. The reconstitution of cellular immunity against CMV was monitored before and during the period of infusions and for up to 12 weeks after the final infusion. The rearranged genes encoding the T-cell receptor served as markers in evaluating the persistence of the transferred T cells.

Results No toxic effects related to the infusions were observed. Cytotoxic T cells specific for CMV were reconstituted in all patients. In vitro measurements showed that cytotoxic activity against CMV was significantly increased (P<0.001) after the infusions in 11 patients who were deficient in such activity before therapy. The level of activity achieved after the infusions was similar to that measured in the donors. Analysis of rearranged T-cell–receptor genes in T cells obtained from two recipients indicated that the transferred clones persisted for at least 12 weeks. Cytotoxic-T-cell activity declined in patients deficient in CD4+ T-helper cells specific for CMV, suggesting that helper-T-cell function is needed for the persistence of transferred CD8+ T cells. Neither CMV viremia nor CMV disease developed in any of the 14 patients.

Conclusions The transfer of CMV-specific clones of CD8+ T cells derived from the bone marrow donor is a safe and effective way to reconstitute cellular immunity against CMV after allogeneic marrow transplantation.

Source Information

From the Fred Hutchinson Cancer Research Center (E.A.W., P.D.G., M.J.G., K.S.W., E.D.T., S.R.R.) and the Departments of Immunology (P.D.G., R.J.F.) and Medicine (P.D.G., E.D.T., S.R.R.), University of Washington, Seattle.

Address reprint requests to Dr. Riddell at the Fred Hutchinson Cancer Research Center, Mailstop M758, 1124 Columbia St., Seattle, WA 98104.

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Anticytomegalovirus T-Cell Clones
Locatelli F., Maccario R., Gerna G., Walter E. A., Greenberg P. D., Riddell S. R.
Extract | Full Text  
N Engl J Med 1996; 334:601, Feb 29, 1996. Correspondence

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• Springer, K. L., Chou, S., Li, S., Giller, R. H., Quinones, R., Shira, J. E., Weinberg, A. (2005). How Evolution of Mutations Conferring Drug Resistance Affects Viral Dynamics and Clinical Outcomes of Cytomegalovirus-Infected Hematopoietic Cell Transplant Recipients. J. Clin. Microbiol. 43: 208-213 [Abstract] [Full Text]  
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• Wang, Z., La Rosa, C., Mekhoubad, S., Lacey, S. F., Villacres, M. C., Markel, S., Longmate, J., Ellenhorn, J. D. I., Siliciano, R. F., Buck, C., Britt, W. J., Diamond, D. J. (2004). Attenuated poxviruses generate clinically relevant frequencies of CMV-specific T cells. Blood 104: 847-856 [Abstract] [Full Text]  
• Parkhurst, M. R., Riley, J. P., Igarashi, T., Li, Y., Robbins, P. F., Rosenberg, S. A. (2004). Immunization of Patients with the hTERT:540-548 Peptide Induces Peptide-Reactive T Lymphocytes That Do Not Recognize Tumors Endogenously Expressing Telomerase. Clin. Cancer Res. 10: 4688-4698 [Abstract] [Full Text]  
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• Kotloff, R. M., Ahya, V. N., Crawford, S. W. (2004). Pulmonary Complications of Solid Organ and Hematopoietic Stem Cell Transplantation. Am. J. Respir. Crit. Care Med. 170: 22-48 [Abstract] [Full Text]  
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