ONCOGENE TRANSFORMATION CAN INDUCE TOLEROGENICITY IN MURINE MACROPHAGES AFTER DOWN-REGULATION OF IMMUNOGENICITY WITHOUT ALTERING MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGEN EXPRESSION

In vitro studies on cell lines may allow analyses of the mechanisms of immunogenicity and tolerogenicity in cells. We used a model of oncoge nic transformation of an established murine macrophage cell line and r eport here that one v-mos-transformed clone expressing unaltered high amounts of MHC class I and II antigens does not induce proliferation o f unprimed T cells in primary mixed lymphocyte reactions, in sharp con trast to its non-transformed parental cells. Interestingly, this clone induces specific unresponsiveness, as revealed by the lack of respons iveness of MHC-specific T cells when subsequently exposed to the perti nent MHC alloantigens in immunogenic form but unaltered MHC-third part y responsiveness of the naive spleen T cells. Furthermore, the accesso ry function of this clone is strongly reduced. These functional defect s could be overcome by the addition of exogenous interleukin-1alpha (I L-1alpha). Analysis of mRNA expression showed a significant and select ive reduction of IL-1alpha mRNA levels when compared with parental cel ls.