Cytotoxic T Lymphocytes to Murine Plasmacytoma Cells in Allogeneic and Syngeneic Mice: H-2 Antigens Are Essential in the Induction and Effector Stages of Ctl

Abstract

Abstract T cell-mediated cytotoxicity and transplantation immunity to immunoglobulin-producing and nonproducing mouse plasmacytoma cells have been investigated in allogeneic and syngeneic mice. By using the 51Cr-release assay it was found that cytotoxic activity was developed in vitro by culturing C57BL/6 spleen cells with immunoglobulin-producing plasmacytoma MOPC 11 (producer) cells that were susceptible to lysis by C57BL/6 anti-BALB/c cytotoxic T lymphocytes (CTL). In contrast, CTL were not induced when C57BL/6 spleen cells were cultured in vitro with immunoglobulin-nonproducing variant cells of MOPC 11 (nonproducer) that contained fewer H-2 antigens as revealed by the cytotoxic responses and cold inhibition tests of C57BL/6 anti-BALB/c CTL. MOPC 11 producer cells, when injected i.p. into C57BL/6 mice, were completely rejected, but the tumor was developed in C57BL/6 mice that had been previously inoculated with MOPC 11 nonproducer cells. When spleen cells from BALB/c mice that had been sensitized in vivo with MOPC 11 producer cells were restimulated in vitro with MOPC 11 producer cells, CTL could be generated to the tumor-associated antigens (TAA) of MOPC 11 producer cells. No syngeneic CTL were induced against MOPC 11 nonproducer cells. Transplantation analyses showed that, although the anti-tumor immunity against MOPC 11 producer cells was observed when BALB/c mice were primed with MOPC 11 producer cells, MOPC 11 nonproducer cells failed to prime BALB/c mice either to MOPC 11 producer or nonproducer cells. The cytotoxic activity of syngeneic CTL generated against MOPC 11 producer cells was significantly inhibited by anti-H-2d serum, suggesting the involvement of H-2 antigens on the membrane of MOPC 11 producer cells in lysis by anti-TAA CTL. These findings, therefore, indicate: 1) H-2 antigens and TAA present on plasmacytoma cells are essential in the induction and effector stages of CTL and 2) H-2 restriction of CTL exists also in plasmacytoma systems.