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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.
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