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You searched for +publisher:"University of Louisville" +contributor:("Kosiewicz, Michele Marie"). Showing records 1 – 2 of 2 total matches.

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University of Louisville

1. Tucker, Colleen. A role for regulatory T cells in gender-biased disease susceptibility to murine lupus.

Degree: PhD, 2010, University of Louisville

Females are more susceptible to autoimmune disease than males. In several mouse models of disease, castration of males exacerbates disease while androgen treatment ameliorates disease. These data suggest hormones can have an influence on disease susceptibility and progression. Regulatory T cells (Tregs), particularly the CD4+CD25+ Tregs, have been shown to be important in controlling autoimmune disease. Studies have shown that depleting regulatory T cells can cause severe autoimmune disease, and increasing regulatory T cell population size can protect from disease. We hypothesized that gender differences in regulatory T cell populations would correlate with differences in disease susceptibility. We used a spontaneous mouse model of systemic lupus erythematosus, (NZBxNZW)F1 (BWF1), in which only females develop full-blown kidney disease to investigate gender differences in regulatory T cell percentages and function between females and males and their relationship to disease development. First, we assessed differences in regulatory T cell function and number between young (before disease onset) female mice from four different strains, two autoimmune-prone strains, BWF1 and SJL, and two more autoimmune-resistant strains, CS7BL/6 and BALB/c. We found no differences in in vitro suppressive function by CD4+CD2S+ Tregs from any of the four strains when co-cultured with either syngeneic CD4+CD2Y responders and APCs or CS7BL/6 CD4+CD2Y responders and APCs. We did, however, find lower percentages of CD4+ cells that expressed Foxp3 (CD4+Foxp3+ cells) in the periphery of BWF1 mice when compared to the other three strains of mice. The CD4+CD2S+CDI03+ cells are a potent memory/effector subset of regulatory T cells that are better suppressors than CD4+CD2S+CDI03- Tregs both in vitro and in vivo. As found with the CD4+CD2S+ Tregs, we also found no differences in the suppressive function of CD4+CD2S+CD103+ cells from any of the four strains of mice. However, percentages of CD4+CD2S+CDI03+ cells were, again, decreased in the periphery of BWF1 mice compared to the other three strains. We found that reduced percentages of both CD4+Foxp3+ and CD4+CD2S+CD103+ cells in the periphery of BWF1 mice were not due to defects in either thymic production or homeostatic proliferation of these cells. These data suggest that it may be the decreased Treg:Teffector cell ratio, and not a defect in inherent suppressive function, that render BWF1 mice more susceptible to autoimmune disease. We next examined gender differences in regulatory T cell function and number between young female and male mice of the four strains. We found no differences in the suppressive ability of either CD4+CD25+ or CD4+CD25+CD103+ Tregs between females and males of any strain. BWF1mice were the only strain in which females had lower peripheral percentages of CD4+Foxp3+ cells than strain-matched males. Strikingly, females of all four strains had lower percentages of CD4+CD25+CD103+ cells in the periphery compared to strain-matched males. The lower percentages did not appear… Advisors/Committee Members: Kosiewicz, Michele Marie.

Subjects/Keywords: Systemic lupus erythematosus; Autoimmunity; Regulatory T cells; Sex differences; CD103

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Tucker, C. (2010). A role for regulatory T cells in gender-biased disease susceptibility to murine lupus. (Doctoral Dissertation). University of Louisville. Retrieved from 10.18297/etd/1465 ; https://ir.library.louisville.edu/etd/1465

Chicago Manual of Style (16th Edition):

Tucker, Colleen. “A role for regulatory T cells in gender-biased disease susceptibility to murine lupus.” 2010. Doctoral Dissertation, University of Louisville. Accessed May 07, 2021. 10.18297/etd/1465 ; https://ir.library.louisville.edu/etd/1465.

MLA Handbook (7th Edition):

Tucker, Colleen. “A role for regulatory T cells in gender-biased disease susceptibility to murine lupus.” 2010. Web. 07 May 2021.

Vancouver:

Tucker C. A role for regulatory T cells in gender-biased disease susceptibility to murine lupus. [Internet] [Doctoral dissertation]. University of Louisville; 2010. [cited 2021 May 07]. Available from: 10.18297/etd/1465 ; https://ir.library.louisville.edu/etd/1465.

Council of Science Editors:

Tucker C. A role for regulatory T cells in gender-biased disease susceptibility to murine lupus. [Doctoral Dissertation]. University of Louisville; 2010. Available from: 10.18297/etd/1465 ; https://ir.library.louisville.edu/etd/1465


University of Louisville

2. Nebane-Ambe, Lum Doreen, 1975-. Sex-based differences in regulatory T cells.

Degree: PhD, 2005, University of Louisville

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 levels in intact females. Moreover, male NZB x NZW mice have more potent and greater numbers of CD4+CD25+CD103+ cells. Androgen deprivation in males led to an increase in disease as indicated by the increase in antibodies to dsDNA and a coincident reduction in CD4+CD25+ cell numbers. On the other hand, the… Advisors/Committee Members: Kosiewicz, Michele Marie.

Subjects/Keywords: T cells; Gender differences; Autoimmune diseases; CD4+CD25+

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Nebane-Ambe, Lum Doreen, 1. (2005). Sex-based differences in regulatory T cells. (Doctoral Dissertation). University of Louisville. Retrieved from 10.18297/etd/1045 ; https://ir.library.louisville.edu/etd/1045

Chicago Manual of Style (16th Edition):

Nebane-Ambe, Lum Doreen, 1975-. “Sex-based differences in regulatory T cells.” 2005. Doctoral Dissertation, University of Louisville. Accessed May 07, 2021. 10.18297/etd/1045 ; https://ir.library.louisville.edu/etd/1045.

MLA Handbook (7th Edition):

Nebane-Ambe, Lum Doreen, 1975-. “Sex-based differences in regulatory T cells.” 2005. Web. 07 May 2021.

Vancouver:

Nebane-Ambe, Lum Doreen 1. Sex-based differences in regulatory T cells. [Internet] [Doctoral dissertation]. University of Louisville; 2005. [cited 2021 May 07]. Available from: 10.18297/etd/1045 ; https://ir.library.louisville.edu/etd/1045.

Council of Science Editors:

Nebane-Ambe, Lum Doreen 1. Sex-based differences in regulatory T cells. [Doctoral Dissertation]. University of Louisville; 2005. Available from: 10.18297/etd/1045 ; https://ir.library.louisville.edu/etd/1045

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