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 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.
Wottge
H U
HU
Institute of Immunology, Christian-Albrechts-Universität, Kiel, Germany.
Eckstein
V
V
Seliger
B
B
Müller-Ruchholtz
W
W
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002999:Clone Cells; D015536:Down-Regulation; D005260:Female; D016258:Genes, mos; D006649:Histocompatibility Antigens / Q000096:biosynthesis*; D007108:Immune Tolerance; D007375:Interleukin-1 / Q000378:metabolism*; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014170:Transformation, Genetic
D006649:Histocompatibility Antigens; D007375:Interleukin-1; D012333:RNA, Messenger