Journal of Experimental Medicine, Vol 179, 1205-1214, Copyright © 1994 by Rockefeller University Press

ARTICLES

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

L Ramarathinam, M Castle, Y Wu and Y Liu
Michael Heidelberger Division of Immunology, Department of Pathology, New York University Medical Center, New York 10016.

A successful antitumor T cell immune response involves induction, recruitment, 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 B7/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. However, unlike the previous reports on melanoma cell lines, B7/BB1- transfected J558 cells fail to induce cross-protection against parental J558 cells. The B7/BB1-transfected (J558-B7), but not untransfected J558 cells (J558-Neo) induce a CD8 T cell-dominant inflammatory response, and the T cells isolated from the tumor infiltrating lymphocytes (TIL) are polyclonal in terms of their T cell receptor V beta usage. Most surprisingly, the freshly prepared TIL have a potent, CD8 T cell-mediated cytotoxicity on tumor cells without any in vitro stimulation. The cytotoxic T lymphocyte (CTL) activity can be blocked by anti-CD8 monoclonal antibody (mAb). Interestingly, the CTL lyse J558- B7 about 10- to 80-fold more efficiently than untransfected J558-Neo cells. This preferential lysis cannot be attributed to recognition of B7/BB1-derived antigen by the T cells. This finding, together with the lack of the cross-protection between the J558-B7 and J558-Neo, suggests that B7/BB1 can also function at the effector phase of CTL responses. This notion is confirmed by our findings that the lysis of J558-B7 can be blocked by anti-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 recruitment and effector function. This conclusion has significant implications for immunotherapy of tumors.
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