Drug-induced in vitro tolerance to allogeneic antigens. I. Establishment of a tolerance induction system in a fully allogeneic murine combination.
C3H/HeSlc (H-2k) spleen cells were cultured with mitomycin C (MMC)-treated C57BL/6CrSlc (H-2b) spleen cells for 2 days and incubated with 5-fluorouracil (5-FU) for a further 9 hr. Thereafter, those C3H/He spleen cells were recultured with the same allogeneic cells for 5 days. Cell-mediated cytotoxicity (CMC) and mixed lymphocyte reaction (MLR) were profoundly suppressed, antigen-specifically, in such C3H/He spleen cells. In contrast, interleukin 2(IL-2) production was not impaired in the restimulating mixed lymphocyte culture (MLC) with C57BL/6. Moreover, an adequate amount of exogenous IL-2 added to the restimulating MLC did not lead to a restoration of the depressed CMC. Suppressor cell activity in the CMC assay was not detected in the C3H/He spleen cells exposed to such a tolerance induction. These results suggest that the unresponsiveness to alloantigens in CMC and MLR was induced through a clonal deletion mechanism, and there may exist a 5-FU-resistant--thus less-proliferative--cell population that can produce IL-2 even after the tolerance induction.
D000818:Animals; D004351:Drug Resistance; D005472:Fluorouracil / Q000494:pharmacology*; D006183:H-2 Antigens / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects*; D007376:Interleukin-2 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000276:immunology; D008811:Mice, Inbred DBA / Q000276:immunology; D013154:Spleen / Q000166:cytology
D006183:H-2 Antigens; D007376:Interleukin-2; D005472:Fluorouracil