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 (EBV) is strongly associated with undifferentiated nasopharyngeal carcinoma. Immunologically, this neoplasia is characterized by the absence of anti-EBV circulating cytotoxic T lymphocytes (CTL), despite a high number of peripheral activated CD8⁺ cells, as previously determined in our laboratory. In order to determine whether the absence of anti-EBV CTL is related to a reduced number of circulating anti-EBV effector cells, we attempted to expand these hypothetical specific T cells by induction of proliferation with recombinant interleukin-2 (rIL-2), in the, absence of any stimulator cells. Optimal conditions for stimulation of peripheral blood lymphocytes (PBL) of nasopharyngeal patients were obtained with 100 U/ml rIL-2 during 10 days of culture. PBL treated with rIL-2 induced a selective expansion of CD8⁺ cells and generated a potent 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 antibodies anti-(HLA class I) and anti-(HLA class II) were inefficient in inhibiting this cytotoxicity. Interestingly, purified CD8⁺ cells acquired the capacity for non-MHC-restricted cytolysis.This work was supported by grant MD7/91/FMT from La Fondation Nationale de la Recherche Scientifique Tunis, Tunisia.