Sex-based differences in regulatory T cells.

T cells;Gender differences;Autoimmune diseases;CD4+CD25+

Lum Doreen Nebane-Ambe, 1975-

University:University of Louisville

Department:Microbiology and Immunology

关键词: T cells;    Gender differences;    Autoimmune diseases;    CD4+CD25+;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=2044&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

Females have a higher incidence of autoimmune diseases than males for reasons that are currently unknown. CD4+CD25+ regulatory T cells play an important role in the maintenance of immunological homeostasis and self-tolerance by suppressing autoreactive T cells that could potentially cause autoimmune diseases. Given that autoimmune diseases are more prevalent in women compared to men, we hypothesized that sex steroids could influence the incidence and/or progression of autoimmune disease through an effect on CD4+CD25+ regulatory T cell number and/or function. The overall objective of this project was then to determine whether sex steroids mediate sex-based differences in CD4+CD25+ regulatory T cell number, function and phenotype, and through this mechanism influence the differential incidence of systemic lupus erythematosus in females and males. To attain our objectives, we 1) assessed the influence of androgens (dihydrotestosterone) on CD4+CD25+ regulatory T-cell number, phenotype and function; 2) assessed the influence of estrogens (estradiol) on CD4+CD25+ regulatory T cell number and function; 3) assessed CD4+CD25+ T cells and the effects of androgens in an animal model of systemic lupus erythematosus (SLE). We found that androgens increased the numbers of CD4+CD25+, CD4+CD25+CD103+ and CD4+CD25+CTLA4+ cells. Moreover, male CD4+CD25+CD103+ cells expressed more of the regulatory cell-associated transcription factor, Foxp3, than females, which also correlated with an enhancement in in vitro regulatory function, because male CD4+CD25+ and CD4+CD25+CD103+ cells suppressed the proliferation of responder CD4+CD25- cells better than those from females. Conversely, estrogens had a very little effect on regulatory T cell numbers, phenotype and function. Our conclusion was that androgens, but not estrogens, can in fact, have an influence on the numbers, function and phenotype of CD4+CD25+ regulatory T cells. In radiation bone marrow chimera experiments, we determined that androgens increase CD4+CD25+ regulatory cell numbers through an effect on the thymic epithelium, but influence the development of CD4+CD25+ regulatory function through a direct effect on the bone marrow-derived precursor (not mature) cells. In the second part of our project, we assessed CD4+CD25+ T cells and the effects of androgens in a murine model of systemic lupus erythematosus (NZB x NZW) in which only females get disease, and found that female NZB x NZW mice had significantly lower levels of CD4+CD25+ and CD4+CD25+CD103+ T cells compared with male mice. Furthermore, androgen deprivation (castration) led to a reduction in the percentages of CD4+CD25+CD103+ cells in male mice to levels lower than those found in intact male mice, or comparable to