Sex-based differences in regulatory T cell responses

调节性 T 细胞反应的性别差异

• 批准号: 6759286
• 负责人: MICHELE M KOSIEWICZ
• 金额: $ 10.73万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6759286
• 关键词: MHC class II antigen; T cell receptor; T lymphocyte; androgen receptor; antigen presenting cell; autoimmune disorder; bone marrow; developmental immunology; estrogen receptors; gender difference; laboratory mouse; leukocyte activation /transformation; sex hormones; thymus; tissue mosaicism

DESCRIPTION (provided by applicant): Many autoimmune diseases are much more prevalent in women compared to men, and include multiple sclerosis, arthritis and systemic lupus erythematosus. Although the reason for this difference is not currently known, the sex hormones are likely to play a significant role. A population of naturally occurring regulatory T cells, CD4+CD25+ regulatory T cells, has recently been described that is responsible for controlling autoimmune disease in mice. Elimination of this population in mice results in severe multi-organ autoimmune diseases. A homologous population has been found in humans that appears to express similar functional properties, at least, in in vitro assays. Our preliminary results indicate that both quantitative and qualitative differences exist in the CD4+CD25+ regulatory T cell population in adult, but not pre-pubertal, female versus male mice, i.e., CD4+CD25+ regulatory T cell numbers and function are decreased in adult female mice. The central hypothesis of this grant proposal is that sex steroids mediate the gender differences in CD4+ CD25+ regulatory T cells, and through this mechanism may influence the differential expression of autoimmune disease in females versus males. The following specific aims are designed to test this hypothesis: I) Characterization of CD4+CD25+ regulatory T cells in female and male mice; 2) Analysis of sex steroid influences on CD4+CD25+ regulatory T cells; and 3) Identification of the anatomical compartment(s) responsive to sex steroids that influences CD4+CD25+ regulatory T cells. The results of these studies will provide important information that can lead to the development of novel therapies for the prevention and treatment of autoimmune disease.

描述（由申请人提供）：许多自身免疫性疾病 与男性相比，在女性中普遍存在，包括多发性硬化症，关节炎， 和系统性红斑狼疮。虽然这种差异的原因是 目前尚不清楚，性激素可能起着重要作用。一 天然存在的调节性T细胞群，CD 4 + CD 25+调节性T细胞 细胞，最近被描述为负责控制 小鼠自身免疫性疾病。在小鼠中消除该群体导致 严重的多器官自身免疫性疾病。已经发现了一个同源种群 在人类中似乎表达类似的功能特性，至少， 体外测定。我们的初步结果表明，定量和 CD 4 + CD 25+调节性T细胞群中存在定性差异， 成年但非青春期前的雌性与雄性小鼠，即，CD4+CD25+ 调节性T细胞的数量和功能在成年雌性小鼠中降低。的 这项拨款提案的中心假设是，性类固醇介导了 CD 4 + CD 25+调节性T细胞的性别差异，并通过这种 机制可能会影响自身免疫性疾病的差异表达， 女性对男性以下具体目标旨在对此进行测试 假设：I）雌性和雌性中CD 4 + CD 25+调节性T细胞的表征 雄性小鼠; 2）分析性类固醇对CD 4 + CD 25+调节性T细胞的影响 细胞;和3）识别响应于 影响CD 4 + CD 25+调节性T细胞的性类固醇。的结果 这些研究将提供重要信息， 开发用于预防和治疗自身免疫性疾病的新疗法 疾病