EFFECT OF CYCLOPHOSPHAMIDE ON LYMPHOKINE PRODUCTION IN MRL LPR YAA MICE/

The Y chromosome (Yaa gene) from autoimmune BXSB mice has been shown t o be responsible for the acceleration of autoimmune symptoms when tran sferred to MRL/lpr mice. We examined the pathological, serological and immunological characteristics of MRL/lpr.Yaa mice and the suppressive effect of cyclophosphamide (CP) on the mice. MRL/lpr.Yaa mice spontan eously developed a massive lymphadenopathy characterized by hypergamma globulinemia, the presence of several autoantibodies, and autoimmune d isease. In MRL/lpr.Yaa mice, IL-2, IL-4 and IL-5 production in concana valin A (Con A)-stimulated splenocytes were about 10-fold lower than i n BALB/c mice at 5 weeks of age. The concentrations of these lymphokin es remained low until the mice were 16 weeks of age. The production of IFN-gamma and IL-6 in 16 week old MRL/lpr.Yaa mice was about 4- and 2 -fold lower, respectively, though these levels were similar in both st rains at 8 weeks of age. It was found that this dysregulation of T cel l function was almost identical to that in MRL/lpr mice. Administratio n of CP to MRL/lpr.Yaa mice ameliorated nephritis, and suppressed prod uction of autoantibodies and the accumulation of abnormal T cells. CP also significantly elevated the production of lymphokines. These findi ngs suggest that an abnormality of T cell function may contribute to t he autoimmune pathogenesis of MRL/Ipr.Yaa mice and that CP probably am eliorates autoimmune disease by improving the T cell functions.