CYTOKINES AND SUPPRESSOR MACROPHAGES CAUSE TUMOR-BEARING HOST CD8+ T-CELLS TO SUPPRESS RECOGNITION OF ALLOGENEIC AND SYNGENEIC MHC CLASS-II MOLECULES

Quantitative and qualitative tumor-associated changes in T cell phenotype and function were identified in CD8+ T cells. Tumor growth changed splenic CD4+/CD8+ T cell ratios and induced the appearance of more cells with the CD8+ phenotype. In comparison to equal concentrations of normal host (NH) counterparts, tumor-bearing host (TBH) CD8+ T cells were highly suppressive to allorecognition and autorecognition. Suppression was not due to quantitative reductions in CD4+ T cells, although minor qualitative differences were observed. Suppression appeared to be mediated partly by prostaglandin E2 (PGE2). Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) contributed to TBH CD8+ T cell-mediated suppression. Blocking studies using monoclonal antibodies (mAb) in conjunction with indomethacin suggested that cytokine networks involving IFN-gamma, IL-4, and PGE2 were disrupted during tumor growth and promoted TBH CD8+ T cell suppression. Alloresponses and autoresponses were significantly suppressed when TBH CD8+ T cells mediated these reactions simultaneously with TBH Ia- macrophages. Inhibition of PGE2 production was unable to reverse the additive suppression caused by these two cell types. These results collectively suggest that tumor-induced changes in CD8+ T cells lead to suppressed allorecognition and autorecognition through both soluble mediator molecules and cellular interactions.