Endogenous CD8+ T cell expansion during regression of monoclonal EBV-associated posttransplant lymphoproliferative disorder.
There are experimental data which suggest that the primary immune effector cell responsible for maintaining immune surveillance against the outgrowth of EBV-transformed B cells in humans is the CTL, but in vivo proof of this is lacking. In this study we perform a series of cellular and molecular assays to characterize an autologous, endogenous immune response against a transplantation-associated, monoclonal, EBV+ posttransplant lymphoproliferative disorder (PTLD). Following allogeneic bone marrow transplantation, a patient developed a monoclonal PTLD of donor B cell origin. With a decrease in immune suppression, we document the emergence of endogenous, donor-derived CD3+CD8+ CTLs, followed by regression of the PTLD. The TCR Vbeta repertoire went from a polyclonal pattern prior to the development of PTLD to a restricted TCR Vbeta pattern during the outgrowth and regression of PTLD. Donor-derived CD3+CD8+ T lymphocytes displayed MHC class I-restricted cytolytic activity against the autologous EBV+ B cells ex vivo without additional in vitro sensitization. The striking temporal relationship between the endogenous expansion of a TCR Vbeta-restricted, CD3+CD8+ population of MHC class I-restricted CTL, and the regression of an autologous monoclonal PTLD, provides direct evidence in humans that endogenous CD3+CD8+ CTLs can be responsible for effective immune surveillance against malignant transformation of EBV+ B cells.
Khatri
V P
VP
Division of Surgery, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Baiocchi
R A
RA
Peng
R
R
Oberkircher
A R
AR
Dolce
J M
JM
Ward
P M
PM
Herzig
G P
GP
Caligiuri
M A
MA
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D011183:Postoperative Complications / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology / Q000821:virology
D016693:Receptors, Antigen, T-Cell, alpha-beta