title: 17β-Estradiol (E-2) administration to male (NZB × SWR)F₁ mice results in increased Id(LN)F₁-reactive memory T-lymphocytes and accelerated glomerulonephritis.
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 17β-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.
authors: Department of Microbiology & Immunology, Cornell University, Ithaca, NY 14853, USA.
authors: F
authors: F
authors: Feng
authors: C J
authors: CJ
authors: Silvin
authors: N C
authors: NC
authors: Fiore
authors: M L
authors: ML
authors: Stoll
authors: K E
authors: KE
authors: Price
authors: P S
authors: PS
authors: Shanley
authors: A E
authors: AE
authors: Silverstone
authors: J
authors: J
authors: Gavalchin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000633:toxicity*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D012737:Sex Factors; D013534:Survival; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D004958:Estradiol