17β-Estradiol (E-2) administration to male (NZB × SWR)F1 mice results in increased IdLNF1-reactive memory T-lymphocytes and accelerated glomerulonephritis

While it has been shown that estradiol treatment accelerates the onset of lupus nephritis with autoantibody production and kidney damage in both male and female lupus-prone mice, the specific mechanism(s) involved are unknown. Our previous work has shown that alterations in IdLNF1-reactive T cells and IdLNF1+ antibodies correlated closely with the onset of autoimmune nephritis in female F1 progeny of SWR and NZB (SNF1) mice, supporting a critical role for the IdLNF1 idiotype in the development of disease. Since male SNF1 mice normally do not develop nephritis, we tested whether administration of 17β-estradiol (E-2) to male SNF1 mice would increase IdLNF1 IgG levels and autoreactive T cells, and further, induce nephritis. We found that E-2-treated male SNF1 mice developed nephritis with the same time course and mean survival as normal female SNF1 mice. Moreover, it appeared that the mechanism involved increased serum IdLNF1+IgG and its deposition in kidney glomeruli, preceded by astriking twofold increase ...