The induction of tolerance and suppression in autoimmune MRL mice using hapten-modified self.
Disturbances in suppressor cell function have been considered important in the pathogenesis of systemic lupus erythematosus (SLE), a conclusion supported by studies with New Zealand mice. To determine whether other SLE mice display similar immunoregulatory defects, we investigated the susceptibility of autoimmune MRL mice to unresponsiveness induced by hapten-modified self (HMS). The response of splenocytes from MRL-lpr/lpr mice (lpr) was compared with those of sex- and age-matched, congenic MRL-+/+ mice (+/+), and H-2-identical (H-2k) CBA/J mice. Spleen cells (NSC) were cultured in vitro with hapten-modified syngeneic splenocytes (TNP-SC) and tested for responsiveness to TNP-LPS (for tolerance) or their ability to suppress the response of fresh cells. There was no difference in the susceptibility of lpr splenocytes from 3- and 10-mo-old mice to the induction of tolerance or suppression when compared with those from age-matched +/+ or CBA mice. To evaluate any quantitative defects in the responsiveness of lpr splenocytes to HMS, we modified the conditions under which suppressor activity was generated. Varying the ratio of NSC to TNP-SC from 10:1 to 2000:1, or changing the concentration of TNBS for haptenation from 10 mM to 0.5 mM per 10(8) spleen cells revealed no differences in the dose-response curves of lpr splenocytes for both tolerance and suppression when compared with those of the CBA. These results indicate that clinically affected MRL mice have intact suppressor cell activity in response to antigen-modified self and suggest a possible therapeutic role of this modality in inducing tolerance to self-antigens.
Santoro, TJ; Scott, DW; Pisetsky, DS
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