Epstein-Barr virus specific T-cell response in NPC biopsies

A close relationship between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC) has been demonstrated by the detection of viral DNA and expression of the latent viral antigens EBNA1 and LMP1-2 in the tumour cells as well as by the presence of high titers of anti-EBV antibodies in the circulation of NPC patients. It is still unknown whether selective homing of active anti-EBV CTL into the tumor takes place and investigations on this subject would shed more light on the role of EBV in NPC carcinogenesis. In this paper, we present a comparative study of anti-EBV cytotoxic activity of tumor infiltrating (TIL) and peripheral blood (PBL) lympocytes towards autologous and HLA-compatible EBV- transformed lymphoblastoid cell lines (LCL). The lymphocyte population within the tumor was characterized by a selective proliferation of T cells expressing activation markers such as the IL-2 receptor and HLA-DR molecules. TIL were devoid of EBV-specific lytic activity although they showed high proportions of CD8 + cells and of lymphocytes expressing the αβ T-cell receptor (TCR αβ). When cultured in the presence of recombinant IL-2 (rIL-2), TIL acquired a cytotoxic activity which was dose and time-dependent. However, the cytotoxicity of these effector cells remained lower than that dipslayed by similarly - treated PBL The lower ability of rIL-2 to induce a lytic activity in TIL was in sharp contrast to the selective proliferation of CD8 + cells in the cultures. The lytic activity acquired by TIL and PBL was non MHC-restricted since it was not inhibited by monoclonal antibodies anti-HLA class I and class II molecules.