INTERLEUKIN-4 PROTECTS AGAINST A GENETICALLY LINKED LUPUS-LIKE AUTOIMMUNE SYNDROME

Interleukin-4 (IL-4) provides support for humoral immune responses thr ough upregulation of T helper (Th) type 2 cell differentiation, but it is not known whether IL-4 promotes antibody-mediated autoimmune disea ses such as systemic lupus erythematosus (SLE). Here, we show that the constitutive expression of an IL-4 transgene by B cells completely ly prevents the development of lethal lupus-like glomerulonephritis in t he (NZW x C57BL/6.Yaa)F1 murine model of SLE. This was associated with marked changes in the serum levels of IgG subclasses, rather than in the total levels of anti-DNA antibodies, with a lack of IgG3, a decrea se of IgG2a, and an increase in IgG1 subclasses, and by a strong reduc tion in the serum levels of gp70-anti-gp70 immune complexes. This effe ct of the transgene appears to result from a modulation of the Th1 ver sus Th2 autoimmune response, since the protected mice displayed compar ably modified IgG2a and IgG3 antibody response against exogenous T cel l-dependent antigen, but not against T cell-independent antigens. Thus , IL-4 prevents the development of this lupuslike autoimmune disease, most likely by downregulating the appearance of Th1-mediated IgG subcl asses of autoantibodies such as the IgG3 autoantibodies which have bee n shown to be especially nephritogenic.