Signaling through CD40 enhances cytotoxic T lymphocyte generation by CD8(+) T cells from mice bearing large tumors

Recent studies have demonstrated the importance of CD40/CD154 (CD40L) inter actions for the generation of cell-mediated antitumor immune responses. Her e we show that signaling via CD40 (through the use of the activating anti-C D40 mAb, 1C10) can actually promote the in vitro generation of CTL activity by CD8(+) splenic T cells from mice bearing a large MOPC-315 tumor. Anti-C D40 mAb had to be added at the initiation of the stimulation cultures of tu mor-bearing splenic cells in order to realize fully its potentiating activi ty for cytotoxic T lymphocyte (CTL) generation, suggesting that signaling t hrough CD40 is important at the inductive stage of antitumor cytotoxicity. Moreover, anti-CD40 mAb was found to enhance the expression of the B7-2 (CD 86) and, to a lesser extent, the B7-1 (CD80) costimulatory molecules on B22 0(+) cells (i.e., B cells), and B7-2 and, to a lesser extent, B7-1 molecule s played an important role in the potentiating effect of anti-CD40 mAb for CTL generation by tumor-bearer splenic cells. Furthermore, B220(+) cells we re found to be essential for the potentiating effect of anti-CD40 mAb, as d epletion of B220(+) cells at the inductive stage completely abrogated the a bility of anti-CD40 mAb to enhance CTL generation. Thus, signaling through CD40 enhances CTL generation by CD8(+) T cells from tumor-bearing mice by a mechanism that involves the up-regulation of B7-2 and, to a lesser extent, B7-1 expression on B220(+) cells.