6533b83afe1ef96bd12a7ac2

RESEARCH PRODUCT

Oncogene transformation can induce tolerogenicity in murine macrophages after down-regulation of immunogenicity without altering major histocompatibility complex antigen expression.

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In vitro studies on cell lines may allow analyses of the mechanisms of immunogenicity and tolerogenicity in cells. We used a model of oncogenic transformation of an established murine macrophage cell line and report here that one v-mos-transformed clone expressing unaltered high amounts of MHC class I and II antigens does not induce proliferation of unprimed T cells in primary mixed lymphocyte reactions, in sharp contrast to its non-transformed parental cells. Interestingly, this clone induces specific unresponsiveness, as revealed by the lack of responsiveness of MHC-specific T cells when subsequently exposed to the pertinent MHC alloantigens in immunogenic form but unaltered MHC-third party responsiveness of the naive spleen T cells. Furthermore, the accessory function of this clone is strongly reduced. These functional defects could be overcome by the addition of exogenous interleukin-1 alpha (IL-1 alpha). Analysis of mRNA expression showed a significant and selective reduction of IL-1 alpha mRNA levels when compared with parental cells.