Different Roles of the CD2 and LFA-1 T-Cell Co-receptors for Regulating Cytotoxic, Proliferative, and Cytokine Responses of Human Vγ9/Vδ2 T Cells

Abstract

Background: Human Vγ9/Vδ2 T lymphocytes recognize nonpeptidic antigens in a manner distinct from the classical antigen recognition by aβ T cells. The apparent lack of major histocompatibility (MHC) restriction and antigen processing allows very fast responses against pathogenic insults. To address the potential functional requirement for accessory molecules, we investigated the roles of the CD2 and lymphocyte function-associated antigen (LFA)-1 T-cell co-receptors in antigen-induced activities of human Vγ9/Vδ2 T-cell clones. Materials and Methods: Human peripheral blood Vγ9/Vδ2 T lymphocytes were cloned and their cytotoxicity against Daudi lymphoma was measured by a standard 51Cr-release assay. The responses of Vγ9/Vδ2 T lymphocytes to nonpeptidic antigens were assessed using DNA synthesis and cytokine ELISA assays. Monoclonal antibodies specific for various molecules with potential T-cell accessory functions were utilized in blocking assays. Results: All of our Vγ9/Vδ2 T-cell clones displayed the Th1 phenotype. The anti-LFA-1 antibody strongly inhibited the cytotoxicity of Vγ9/Vδ2 T cells against Daudi B-cell lymphoma; whereas, it had no influence on the antigen-induced cytokine release or proliferation. In contrast, antibodies against CD2 and LFA-3 had no effect on the lytic activity of Vγ9/Vδ2 T cells, but strongly inhibited the cytokine release and proliferation. However, the CD2-LFA-3 interaction was not an absolute requirement for the cytokine release and the DNA synthetic activity of antigen-stimulated Vγ9/Vδ2 T cells, since the inhibitory effect could be reversed by addition of exogenous interleukin 2 (IL-2). Conclusions: These novel observations indicate that the signals generated by different accessory molecules and IL-2 can contribute in an integrated fashion to the regulation of Vγ9/Vδ2 T cells. These interactions may be important for the effectiveness of Vγ9/Vδ2 T-cell responses.