IL-10 CONVERTS MOUSE LYMPHOMA-CELLS TO A CTL-RESISTANT, NK-SENSITIVE PHENOTYPE WITH LOW BUT PEPTIDE-INDUCIBLE MHC CLASS-I EXPRESSION

IL-10 has a variety of effects including: inhibition of monocyte MHC c lass Ii-dependent Ag presentation, Th1 cytokine production, and inhibi tion of T cell proliferation. Recently we have shown that IL-10 inhibi ts Ag presentation to human tumor-specific and allospecific CTL. In th e present study we showed that transfection of the mouse lymphoma RMA (H-2(b)) with the IL-10 gene induced conversion to a RMA-S-like phenot ype. The changes included an inhibition of lysis by minor histocompati bility or tumor Ag-specific CTLs and, conversely, a dramatic increase in susceptibility to lysis by NK cells. The RMA-10 transfectants showe d levels of H-2 expression as low or even lower than those found on RM A-S. The levels of tested adhesion molecules were unaltered. Treatment of RMA with rIL-10 gave a less pronounced change in phenotype. In add ition, relative to untreated target cells, IL-10 pretreated cells or I L-10 transfectants were unaltered in their capacity to affect cytotoxi city by cold target inhibition, arguing against the possibility that t he observed effect could be a direct effect of IL-10 on the CTL. The e xpression of H-2 was partially restored by coculturing RMA-10 transfec tants with class I-binding peptides. Taken together, these results ind icate that IL-10 exerts a post-transcriptional effect on H-2 expressio n, compatible with an induced decrease in the access of peptides to th e MHC class I complex. IL-10 is the first cytokine reported to have th is effect and also the first factor shown to induce NK sensitivity and reduced sensitivity to CTL, an effect that may be of physiologic rele vance.