EMERGENCE OF NON-MAJOR-HISTOCOMPATIBILITY-COMPLEX-RESTRICTED LYTIC CD8+ CELLS IN THE BLOOD OF NASOPHARYNGEAL CARCINOMA PATIENTS

A large body of evidence has suggested that the Epstein-Barr virus (EB V) is strongly associated with undifferentiated nasopharyngeal carcino ma. Immunologically, this neoplasia is characterized by the absence of anti-EBV circulating cytotoxic T lymphocytes (CTL), despite a high nu mber of peripheral activated CD8+ cells, as previously determined in o ur laboratory. In order to determine whether the absence of anti-EBV C TL is related to a reduced number of circulating anti-EBV effector cel ls, we attempted to expand these hypothetical specific T cells by indu ction of proliferation with recombinant interleukin-2 (rIL-2), in the, absence of any stimulator cells. Optimal conditions for stimulation o f peripheral blood lymphocytes (PBL) of nasopharyngeal patients were o btained with 100 U/ml rIL-2 during 10 days of culture. PBL treated wit h rIL-2 induced a selective expansion of CD8+ cells and generated a po tent cytotoxicity towards autologous or HLA-compatible lymphoblastoid cell lines, used as target cells in a chromium-release thest. However, this cytolysis was non-MHC-restricted, since, the monoclonal antibodi es anti-(HLA class I) and anti-(HLA class II) were inefficient in inhi biting this cytotoxicity. Interestingly, purified CD8+ cells acquired the capacity for non-MHC-restricted cytolysis.