Different roles of the CD2 and LFA-1 T-cell co-receptors for regulating cytotoxic, proliferative, and cytokine responses of human V gamma 9/V delta 2T cells

Background: Human V gamma 9/V delta 2 T lymphocytes recognize nonpeptidic a ntigens in a manner distinct From the classical antigen recognition by crp T cells. The apparent lack of major histocompatibility (MHC) restriction an d antigen processing allows very fast responses against pathogenic insults. To address the potential functional requirement for accessory molecules, w e investigated the roles of the CD2 and lymphocyte function-associated anti gen (LFA)-1 T-cell co-receptors in antigen-induced activities of human V ga mma 9/V delta 2 T-cell clones. Materials and Methods: Human peripheral blood V gamma 9/V delta 2 T lymphoc ytes were cloned and their cytotoxicity against Daudi lymphoma was measured by a standard Cr-51-release assay. The responses of V gamma 9/V delta 2 T lymphocytes to nonpeptidic antigens were assessed using DNA synthesis and c ytokine ELISA assays. Monoclonal antibodies specific for various molecules with potential T-cell accessory functions were utilized in blocking assays. Results: All of our V gamma 9/V delta 2 T-cell clones displayed the Th1 phe notype. The anti-LFA-1 antibody strongly inhibited the cytotoxicity of V ga mma 9/V delta 2 T cells against Daudi B-cell lymphoma; whereas, it had no i nfluence on the antigen-induced cytokine release or proliferation. In contr ast, antibodies against CD2 and LFA-3 had no effect on the lytic activity o f V gamma 9/V delta 2 T cells, but strongly inhibited die cytokine release and proliferation. However, the CD2-LFA-3 interaction was not an absolute r equirement for the cytokine release and the DNA synthetic activity of antig en-stimulated V gamma 9/V delta 2 T cells, since the inhibitory effect coul d be reversed by addition of exogenous interleukin 2 (IL-2). Conclusions: These novel observations indicate that the signals generated b y different accessory molecules and IL-2 can contribute in an integrated fa shion to the regulation of V gamma 9/V delta 2 T cells. These interactions may be important for the effectiveness of V gamma 9/V delta 2 T-cell respon ses.