Suppression of antigen-specific interleukin 2 production in the MRL/MpJ-lpr/lpr mouse.
Several murine strains with spontaneously occurring systemic lupus erythematosus-like disease demonstrate defects in immunoregulation. The MRL/MpJ-lpr/lpr (MRL-1) strain develops a severe age-progressive defect in interleukin 2 (IL 2) production in response to mitogen or antigen. In this study, we demonstrate in vitro the presence of suppressor cells in the lymph nodes of naive mice of the MRL background. Suppression by MRL-1 lymph node cells was partially reversed by treatment with anti-Lyt-1.2 monoclonal antibody and complement and was moderately radiosensitive. Suppression by lymph node cells from the congenic MRL/MpJ-+/+ (MRL-+) mouse was somewhat more resistant to treatment with anti-Lyt-1.2 and complement, or radiation. Lymph node cells from the H-2-syngeneic mouse strain, C3H/HeJ, failed to suppress. Thus, lymph nodes from mice of the MRL background contain cells capable of suppressing in vitro IL 2 responses. We next performed cell transfers to determine whether suppressor cells contribute in vivo to the IL 2 defect. Lymph node cells, but not spleen cells, from MRL-1 mice by 5 to 6 mo of age suppressed antigen-specific IL 2, CTL, and DTH responses when transferred into young MRL-+ recipients. Transfer of identical numbers of lymph node cells from age-matched MRL-+ mice failed to suppress IL 2 production. Transfer of suppression was sensitive to treatment with monoclonal anti-Lyt-2.1 and complement, and to 250 rad of radiation. Thus, this study suggests a role for active suppression of IL 2 production in the establishment of the IL 2 defect in the MRL-1 mouse. Further, suppression may involve phenotypically distinct T lymphocyte subpopulations.
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D000375:Aging; D000818:Animals; D000950:Antigens, Ly; D002470:Cell Survival; D000939:Epitopes / Q000276:immunology*; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000096:biosynthesis*; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000528:radiation effects; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology* / Q000528:radiation effects
D000950:Antigens, Ly; D000939:Epitopes; D007376:Interleukin-2