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Endogenous CD8⁺ T Cell Expansion During Regression of Monoclonal EBV-Associated Posttransplant Lymphoproliferative Disorder¹

Vijay P. Khatri^2,*, Robert A. Baiocchi^2,§, Ruoqi Peng^§, Adam R. Oberkircher, Jean M. Dolce, Pamela M. Ward, Geoffrey P. Herzig^§ and Michael A. Caligiuri^3,§

Divisions of ^* Surgery, Medicine, and Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263; and ^§ Division of Hematology/Oncology and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210

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 Vß repertoire went from a polyclonal pattern prior to the development of PTLD to a restricted TCR Vß 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 Vß-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.

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