Title: 17ýý-Estradiol (E-2) administration to male (NZB ýý SWR)Fýýý mice results in increased Id(LN)Fýýý-reactive memory T-lymphocytes and accelerated glomerulonephritis.
Authors: Feng, F; Silvin, C J; Fiore, N C; Stoll, M L; Price, K E; Shanley, P S; Silverstone, A E; Gavalchin, J
Published In Lupus, (2012 Mar)
Abstract: 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 Id(LN)F(1)-reactive T cells and Id(LN)F(1)+ antibodies correlated closely with the onset of autoimmune nephritis in female F(1) progeny of SWR and NZB (SNF(1)) mice, supporting a critical role for the Id(LN)F(1) idiotype in the development of disease. Since male SNF(1) mice normally do not develop nephritis, we tested whether administration of 17ýý-estradiol (E-2) to male SNF(1) mice would increase Id(LN)F(1) IgG levels and autoreactive T cells, and further, induce nephritis. We found that E-2-treated male SNF(1) mice developed nephritis with the same time course and mean survival as normal female SNF(1) mice. Moreover, it appeared that the mechanism involved increased serum Id(LN)F(1)(+)IgG and its deposition in kidney glomeruli, preceded by a striking twofold increase in T-lymphocytes expressing the memory phenotype (CD44(+)CD45RB(lo)) predominantly in the Id(LN)F(1)-reactive T-cell population. In addition, we noted that cells with this phenotype were increased in the nephritic kidneys of treated mice, suggesting a direct involvement of those cells in the renal pathology. E-2 treatment also induced increased numbers of pathogenic Id(LN)F(1)+ antibody-producing B cells and elevated presentation of pathogenic Id(LN)F(1)+ peptide. Taken together, these results suggest a mechanism of E-2-induced acceleration of autoimmune disease in lupus-prone mice may involve expansion of autoreactive idiotypic T and B-cell populations.
PubMed ID: 22065096
MeSH Terms: Animals; Disease Models, Animal; Estradiol/toxicity*; Female; Glomerulonephritis/immunology; Glomerulonephritis/physiopathology*; Immunoglobulin G/blood; Immunoglobulin G/immunology; Immunoglobulin Idiotypes/immunology; Kidney Glomerulus/immunology; Kidney Glomerulus/pathology; Lupus Nephritis/immunology; Lupus Nephritis/physiopathology*; Male; Mice; Mice, Inbred NZB; Sex Factors; Survival; T-Lymphocytes/immunology*; Time Factors