Impairment of allograft tumor immunity by isotype-like suppression of antigen-specific T cell factors.

PCl-F is an antigen-binding factor that is derived from T cells of picryl chloride (PCl) contact-sensitized mice. Intravenous transfer of PCl-F into naive recipients, followed immediately by PCl challenge, results in the ability to elicit an immediate hypersensitivity-like cutaneous response. This PCl-F-dependent early response is an obligatory step in the mediation of a PCl-specific delayed-type hypersensitivity reaction by late-acting, antigen/MHC-restricted effector T cells. These latter cells recruit a local infiltrate of inflammatory cells by producing chemoattractant lymphokines. Injection of PCl-F also induces a T cell-dependent feedback circuit that ultimately suppresses production of PCl-F, and thus suppresses DTH to PCl. This form of regulation is not antigen-specific, since PCl-F induces suppression of DTH to PCl and to other antigens via suppression of the production of antigen-binding T cell factors necessary for initiation of DTH. This form of regulation does not affect classic, late-acting, lymphokine-producing effector T cells of DTH, or helper T cells for antibody responses. We now report that injection of PCl-F is also capable of inducing suppression of cutaneous hypersensitivity responses to allogeneic and syngeneic tumor cells, and of immune resistance to an allogeneic tumor graft. Our results suggest, therefore, that antigen (tumor)-specific T cell factors play a role in initiation of hypersensitivity responses to tumor cells. Injection of PCl-F suppressed, besides tumor-specific cutaneous hypersensitivity, production of the tumor-specific T cell factor that renders macrophages cytotoxic to tumor cells (i.e., specific macrophage-arming factor or SMAF). Thus, PCl-F injection may impair immune resistance to tumor cells by suppressing initiation of hypersensitivity responses that recruit macrophages, and also by inhibiting production of SMAF that renders macrophages cytotoxic. It is therefore tempting to conclude that the antigen-specific T cell factors that initiate DTH, such as PCl-F and SMAF, belong to the same isotype or group of antigen-specific T cell products that can be regulated by a form of feedback suppression that is isotype-like and inhibits production of these related, antigen-specific T cell factors.