Effect of Major Histocompatibility Complex on Deficinent Interleukin 2 Production in Autoimmune-Prone New Zealand Mice

Abstract

Evidence that genetic factors play important roles in the pathogenesis of systemic lupus erythematosus (SLE) was provided by the findings of an association between major histocompatibility complex (MHC) and human and murine SLE, such as NZB and NZB x NZW (B/W) F1 hybrid mice. Recent studies disclosed that a profound defect in the production of interleukin 2 (IL 2) develops in human as well as murine SLE. To investigate the correlations among the IL 2 deficit, MHC and the pathogenesis of SLE, we established MHC (H-2) congenic NZB, B/W F 1 and NZW strains. These include NZB·H- 2 ^d/d, NZB·H-2 ^d/z, NZB·H- 2 ^z/z B/W F 1·H- 2 ^d/d, B/W F1·H-2 ^d/z, B/W F 1·H-2 ^Z/Z, NZW·H-2 ^d/d, NZW·H-2^d/z and NZW·H-2^z/z strains. The results showed that among these steains of mice the deficit of IL 2 production by splenic T cells and the decrease in the number of IL 2 receptor positive T cells were observed only in NZB·H- 2 ^d/d, NZB·H- 2 ^d/z and B/W F 1 H- 2 ^d/zmice. Serum anti-double-stranded (ds) DNA antibodies, a typical clinical SLE feature, were also detected only in these three strains. Therefore, these two SLE features, the defect in the IL 2 production and the synthesis of and-dsDNA antibodies appear to be closely associated with MHC and pathogenetically related. Correlation of the genetic basis between these two SLE features were discussed.