(The FASEB Journal. 2008;22:lb476)
© 2008 FASEB
Age-related changes in regulatory cell populations and function in lupus-prone mice
Colleen Field Tucker,
Pascale Alard,
Sarah A Parnell,
Jean N Manirarora,
Doreen L Nebane-Ambe and
Michele M Kosiewicz
Microbiology and Immunology, University of Louisville, Louisville, KY
ABSTRACT
Female BWF1 mice develop systemic lupus erythematosus (SLE). We performed a time-course analysis on CD4+Foxp3+ (Tr) and CD4+CD25+CD103+ (TrCD103) cells in female and male BWF1 mice. Pre-pubertal mice had the same percentages of both Tr and TrCD103 cells. By 9 wks, female mice had decreased percentages of both cell types, and TrCD103 cells were less effective in vitro. High anti-dsDNA antibody levels are first detected in females at 12–16 wks. By 20 wks, the percentages and function of Tr and TrCD103 cells were similar in females and males, however, anti-dsDNA antibody levels in females continued to increase as mice aged. Female mice first develop full-blown kidney disease by 28 wks, and by 34 wks, 50% have disease. Age-matched (>30 wks) disease-free female and male mice had the same percentages of Tr and TrCD103 cells with similar regulatory function in vitro. Surprisingly, sick female mice had increased percentages of both cell types that exhibited potent regulatory function in vitro. These data suggest adequate numbers and optimal function of regulatory cells are important during early stages of disease. However, even large numbers of potent regulatory cells may not be effective at late stages of disease. The reasons for the latter are unclear, but could be due to effector B/T cell resistance to Tr cell control and/or failure of Tr cells to traffic effectively. Supported by the Lupus Research Instit.
