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Blood, 15 October 2000, Vol. 96, No. 8, pp. 2814-2821

IMMUNOBIOLOGY

Rapid reconstitution of Epstein-Barr virus-specific T lymphocytes following allogeneic stem cell transplantation

Natalie A. Marshall, John Greg Howe, Richard Formica, Diane Krause, John E. Wagner, Nancy Berliner, Jill Crouch, Ingrid Pilip, Dennis Cooper, Bruce R. Blazar, Stuart Seropian, and Eric G. Pamer

From the Sections of Infectious Diseases, Medical Oncology, Hematology, and Nephrology and the Departments of Medicine, Immunobiology, and Laboratory Medicine, Yale School of Medicine, New Haven, CT; and the University of Minnesota Cancer Center, the Department of Pediatrics, and the Division of Blood and Marrow Transplantation, Minneapolis, MN.

Epstein-Barr virus (EBV)-specific CD8 T lymphocytes are present at remarkably high frequencies in healthy EBV+ individuals and provide protection from EBV-associated lymphoproliferative diseases. Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a commonly used therapy in which T-cell surveillance for EBV is temporarily disrupted. Herein, human leukocyte antigen (HLA) class I tetramers were used to investigate the reestablishment of the EBV-specific CD8 T-cell repertoire in patients following allo-PBSCT. CD8+ T cells specific for lytic and latent cycle-derived EBV peptides rapidly repopulate the periphery of matched sibling allo-PBSCT patients. The relative frequencies of T cells specific for different EBV peptides in transplantation recipients closely reflect those of their respective donors. Investigation of patients at monthly intervals following unmanipulated allo-PBSCT demonstrated that the frequency of EBV-specific T cells correlates with the number of EBV genome copies in the peripheral blood and that expansion of EBV-specific T-cell populations occurs even in the setting of immunosuppressive therapy. In contrast, patients undergoing T-cell-depleted or unrelated cord blood transplantation have undetectable EBV-specific T cells, even in the presence of Epstein-Barr viremia. The protective shield provided by EBV-specific CD8 T cells is rapidly established following unmanipulated matched sibling allo-PBSCT and demonstrates that HLA class I tetramers complexed with viral peptides can provide direct and rapid assessment of pathogen-specific immunity in this and other vulnerable patient populations.

© 2000 by The American Society of Hematology.
 

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