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: F Feng, C J Silvin, N C Fiore, M L Stoll, K E Price, P S Shanley, A E Silverstone, J Gavalchin
• Journal: Lupus (Lupus) Vol. 21 Issue 3 Pg. 288-301 (Mar 2012) ISSN: 1477-0962 [Electronic] England
• PMID: 22065096 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin G
• Immunoglobulin Idiotypes
• Estradiol

Topics

• Animals
• Disease Models, Animal
• Estradiol (toxicity)
• Female
• Glomerulonephritis (immunology, physiopathology)
• Immunoglobulin G (blood, immunology)
• Immunoglobulin Idiotypes (immunology)
• Kidney Glomerulus (immunology, pathology)
• Lupus Nephritis (immunology, physiopathology)
• Male
• Mice
• Mice, Inbred NZB
• Sex Factors
• Survival
• T-Lymphocytes (immunology)
• Time Factors