AN MRL/MPJ-LPR/LPR SUBSTRAIN WITH A LIMITED EXPANSION OF LPR DOUBLE-NEGATIVE T-CELLS AND A REDUCED AUTOIMMUNE SYNDROME

The autosomal recessive mutant gene, Ipr, has been shown to accelerate the progression of lupus-like autoimmune disease, which is associated with a massive expansion of a unique CD4-CD8- double-negative T cell subset, in MRL/MpJ mice. Here we report a substrain of MRL/MpJ-Ipr/Ipr (MRL-Ipr) mice which live almost twice as long with delayed development of glomerulonephritis, compared with conventional MRL-Ipr mice. This substrain, termed MRL-Ipr.II (II for long-lived), develops generalized lymphadenopathy characteristically seen in MRL-Ipr mice. However, the expansion of a double negative Ipr T cell subset is markedly limited with a mean value of 15% in their lymph nodes compared to about 70% in conventional MRL-Ipr mice. Overall production of autoantibodies, such as anti-DNA and rheumatoid factors, does not significantly differ between the two MRL-Ipr mice. However, serum levels of cryoglobulins, whose major component is IgG3, are markedly diminished in MRL-Ipr.II mice with a parallel decrease in IgG3. Since MRL-Ipr.II mice still carry the Ipr mutation, as documented by the presence of defects in the Fas antigen, a possible new mutation in this substrain may play a significant role in the pathogenesis of lupus-like autoimmune syndrome.