PHORBOL ESTER EFFECTS ON SPLENIC LYMPHOCYTE COMPOSITION AND CYTOTOXICT-CELL ACTIVITIES OF SSIN MICE - A STRAIN DEFICIENT IN CD8(-CELLS() T)

SSIN mice are considerably more sensitive to the effects of 12-O-tetra decanoylphorbol-13-acetate (TPA) in two-stage skin carcinogenesis prot ocols than are most other strains and stocks of mice, Experiments were performed to determine whether there was an immunological basis for t his sensitivity, SSIN mice were haplotyped and found to be H-2(q), T c ells represented similar to 31% of the splenic cellularity of non-trea ted SSIN mice, but similar to 44% in BALB/c, C57BL/6, B6C3F1 and SENCA R mice, Splenic CD4(+)/CD8(+) T cell ratios were similar to 4.2, 2.9, 2.4, 1.8 and 1.7 in SSIN, SENCAR, BALB/c, B6C3F1 and C57BL/6 mice, res pectively, The unusually high ratio in SSIN spleens was the consequenc e of reductions in CD8(+) T cells, The ratio of CD4(+)/CD8(+) T cells in SSIN thymocytes was similiar to that measured in the spleen, The sp lenic cytotoxic T lymphocyte (CTL) activities of the various murine st rains inversely correlated with their splenic CD4(+)/CD8(+) ratios and their sensitivities in two-stage skin carcinogenesis protocols, Repea ted in vivo topical treatment of SSIN mice with TPA caused significant decreases in splenic T cell contents, but affected neither the spleni c CD4(+)/CD8(+) T cell ratio nor the development of a CTL response upo n allogeneic tumor challenge, SSIN mice also had very low splenic natu ral killer cell activities, Furthermore, relative to the other strains of mice, SSIN mice were poor responders upon alloantigen challenge in mixed lymphocyte response assays, These findings demonstrate that SSI N mice differ markedly from other murine stocks and strains in their s plenic lymphocyte composition and in their abilities to mount some MHC -restricted and non-restricted immunosurveillance processes.