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 ass ays to characterize an autologous, endogenous immune response against a tra nsplantation-associated, monoclonal, EBV+ posttransplant lymphoproliferativ e disorder (PTLD). Following allogeneic bone marrow transplantation, a pati ent 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 V beta reper toire went from a polyclonal pattern prior to the development of PTLD to a restricted TCR V beta pattern during the outgrowth and regression of PTLD, Donor-derived CD3(+)CD8(+) T lymphocytes displayed MHC class I-restricted c ytolytic activity against the autologous EBV+ B cells ex vivo without addit ional in vitro sensitization. The striking temporal relationship between th e endogenous expansion of a TCR V beta-restricted, CD3(+)CD8(+) population of MHC class I-restricted CTL, and the regression of an autologous monoclon al PTLD, provides direct evidence in humans that endogenous CD3(+)CD8(+) CT Ls can be responsible for effective immune surveillance against malignant t ransformation of EBV+ B cells.