Early antigen elimination by cytotoxic T cells results in diminished cellular immune responses to allogeneic tumor |
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Authors: | Paul H Sugarbaker Wilbert Matthews |
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Institution: | Surgery Branch, Building 10, Room 10N116, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20205 U.S.A. |
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Abstract: | Previous reports have suggested that repeated alloantigenic challenge increases humoral responses to alloantigens, but may cause decreasing cellular responses. We stimulated BALB/c (H-2d) mice with intraperitoneal EL-4 tumor (H-2b) and serially assessed cytotoxic responses in spleen and peritoneal lymphocytes using 51Cr-labeled EL-4 target cells. We observed that cytotoxicity generated in the spleen of nonimmune BALB/c mice was much greater than that in immunized mice; similar peak responses were generated in peritoneal lymphocytes in normal and immunized hosts. Complement-mediated cytotoxicity was not necessary for diminished splenic responses in hyperimmune hosts, for the same phenomenon was seen in the Hzl anti-BL/6 system which is free of humoral responses. Irradiation (2000 rad) of the EL-4 tumor challenge prevented tumor cell proliferation and markedly reduced splenic responses in nonimmune mice. We suggest that cytotoxic cells suppressed further generation of cyto-toxicity; by effecting an early elimination of tumor inoculum, tumor proliferation was abrogated and dose of cellular antigen was, consequently, markedly reduced. |
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