Induction of apoptosis in Herpesvirus saimiri-immortalized T lymphocytes by blocking interaction of CD28 with CD80/CD86

We have previously shown that Herpesvirus saimiri (HVS) immortalizes primary macaque monkey T lymphocytes, In this study, we examined the characteristics of the immortalized T cells. The cells showed the phenotype of activated T lymphoblasts (CD3(+) CD25(+) CD69(+) MHC-IIDR+) and produced no infectious virus while viral DNA was detected in the Hirt DNA. Interestingly, both a major costimulatory molecule, CD28, and its ligands, CD80/CD86, were coexpressed on the immortalized T cells. The treatment of the cells with a neutralizing monoclonal antibody against CD28, which blocks interaction of CD28 with CD80/CD86, resulted in retarded cell growth and in induction of apoptosis. The effect of the antibody treatment was not overcome by exogenous interleukin-2 treatment. These findings demonstrate the requirement of interaction of CD28 with CD80/CD86 for the optimal growth of HVS-immortalized T cells. (C) 1999 Academic Press.