T-CELL COSTIMULATION BY B7 BB1 INDUCES CD8 T-CELL-DEPENDENT TUMOR REJECTION - AN IMPORTANT ROLE OF B7/BB1 IN THE INDUCTION, RECRUITMENT, AND EFFECTOR FUNCTION OF ANTITUMOR T-CELLS/

A successful antitumor T cell immune response involves induction, recr uitment, and effector function of T cells. While B7/BB1 is known as a major costimulatory molecule in the induction of T cell responses, its role in T cell recruitment and effector function is still unclear. In this study, we show that introducing a major costimulatory molecule B 7/BB1 into a major histocompatibility complex class II-negative tumor cell line, J558, results in a drastic reduction of its tumorigenicity. The tumor rejection depends on CD8 T cells but not CD4 T cells. Howev er, unlike the previous reports on melanoma cell lines, B7/BB1-transfe cted J558 cells fail to induce cross-protection against parental J558 cells. The B7/BB1-transfected (J558-B7), but not untransfected J558 ce lls (J558-Neo) induce a CD8 T cell-dominant inflammatory response, and the T cells isolated from the tumor infiltrating lymphocytes (TIL) ar e polyclonal in terms of their T cell receptor Vbeta usage. Most surpr isingly, the freshly prepared TIL have a potent, CD8 T cell-mediated c ytotoxicity on tumor cells without any in vitro stimulation. The cytot oxic T lymphocyte (CTL) activity can be blocked by anti-CD8 monoclonal antibody (mAb). Interestingly, the CTL lyse J558-B7 about 10- to 80-f old more efficiently than untransfected J558-Neo cells. This preferent ial lysis cannot be attributed to recognition of B7/BB1-derived antige n by the T cells. This finding, together with the lack of the cross-pr otection between the J558-B7 and J558-Neo, suggests that B7/BB1 can al so function at the effector phase of CTL responses. This notion is con firmed by our findings that the lysis of J558-B7 can be blocked by ant i-B7 mAbs. Taken together, our results indicate that not only can the B7/BB1 molecule function as a costimulatory molecule at the initiation of immune response, it can also play a major role in T cell recruitme nt and effector function. This conclusion has significant implications for immunotherapy of tumors.