CD28 is not required for rejection of unmanipulated syngeneic and autologous tumors

Abstract

To gain a better understanding of the requirement of CD28 co-stimulation in different types of T cell-dependent tumor rejection responses, we performed a series of syngeneic and autologous tumor rejection experiments on CD28 knockout mice. In a preimmunization-challenge model, virally-induced ALC lymphoma and methylcholanthrene induced MC57X fibrosarcoma transplants were rejected similarly by syngeneic CD28 knockout and immunocompetent controls. ALC-specific cytotoxic T lymphocytes (CTL) and MC57X-specific tumor necrosis factor (TNF) release were induced in CD28 knockouts, although at a reduced level in the latter case. Secondly, the spontaneous regression of Moloney murine sarcoma virus (MMSV)-induced primary tumors in the autologous hosts occurred equally in CD28 knockouts and in immunocompetent control mice. A comparable virus-specific CTL response was generated in both, as revealed in cytolytic assays against RBL-5 targets. Thirdly, the spontaneous rejection of the B7-transfected EL-4 lymphoma by immunocompetent hosts was abrogated in CD28 knockout mice, since more than 82% CD28 knockouts developed tumors after inoculation with B7-transfected EL-4 cells. Our results therefore show that CD28 co-stimulatory molecules are not required for the rejection of unmanipulated syngeneic tumors in hyperimmunized hosts and the regression of MMSV-induced sarcoma in autochthonous hosts.