CD8aa+ Cells and Ovarian Functions

CD8aa 细胞和卵巢功能

• 批准号: 7144388
• 负责人: YAHUAN LOU
• 金额: $ 24.65万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7144388
• 关键词: active immunization; athymic mouse; cell population study; chemoattractants; chemokine; chemokine receptor; chemotaxis; corpus luteum; cytotoxic T lymphocyte; estrus; fertility immunology; flow cytometry; gene expression; graafian follicles; hormone regulation /control mechanism; luteinizing hormone; microarray technology; ovary; ovulation; recombinant proteins; thymus

DESCRIPTION (provided by applicant): In this application, we proposed to investigate how a novel ovarian CD8aa+ cell population participates in important ovarian functions such as ovulation. Involvement of the immune system in ovarian functions has been recognized. The critical role of the thymus in ovarian functions is well known. Thus, athymic nude female mice are infertile, and thymectomy leads to ovarian dysfunctions. However, it remains unclear how the thymus participates in ovarian functions. We have identified a novel CD8aa+ population in the internal of antral follicles and their dramatic influx into the ovulating follicles during hCG-induced ovulation. This novel CD8aa+ cells probably originate from thymus and involved in important ovarian functions such as ovulation. Thus, transfer of syngeneic thymocytes, which contain several CD8aa+ cell populations, into the female nude mice restored their ovulatory ability. We next identified ovarian expression of chemokine TECK (thymus expressed chemokine) to be critical for the homing and influx of CD8aa+ cells into the ovary during ovulation. Thus, eliciting anti-TECK antibody by active immunization in the female BALB/c mice led to not only diminishment of the ovarian CD8aa+ cells but also infertility in the immunized mice. Based on the above results, we hypothesize a novel relationship between the thymus and the ovarian functions: 1) the novel CD8aa+ cells are originated from the thymus and recruited into the ovary by ovarian TECK, which is under hormonal regulation, and 2) the CD8aa+ cells are critical for ovulation/luteinization. This is intended to test out hypothesis by 1) determination of lineage and phenotype of ovarian CD8aa+, 2) identification of ovarian function that the ovarian CD8aa+ cells participate in, and 3) identification of TECK- expressing ovarian cells and determination of hormonal regulation of TECK expression in the ovary.

描述（由申请人提供）：在本申请中，我们提出研究新的卵巢CD 8aa+细胞群如何参与重要的卵巢功能，如排卵。免疫系统参与卵巢功能已被公认。胸腺在卵巢功能中的关键作用是众所周知的。因此，无胸腺裸鼠是不育的，胸腺切除导致卵巢功能障碍。然而，胸腺如何参与卵巢功能仍不清楚。我们已经确定了一个新的CD 8aa+人口的内部窦卵泡和他们的戏剧性流入排卵卵泡在hCG诱导排卵。这种新的CD 8aa+细胞可能来源于胸腺，并参与重要的卵巢功能，如排卵。因此，将含有几个CD 8aa+细胞群的同基因胸腺细胞转移到雌性裸鼠中恢复了它们的排卵能力。我们接下来鉴定了趋化因子TECK（胸腺表达的趋化因子）的卵巢表达对于排卵期间CD 8aa+细胞归巢和流入卵巢至关重要。因此，通过主动免疫在雌性BALB/c小鼠中引发抗TECK抗体不仅导致卵巢CD 8aa+细胞减少，而且导致免疫小鼠不育。基于上述结果，我们推测胸腺与卵巢功能之间存在一种新的关系：1）新的CD 8aa+细胞来源于胸腺，并通过卵巢TECK募集到卵巢中，卵巢TECK受激素调节; 2）CD 8aa+细胞对排卵/黄体化至关重要。这旨在通过1）确定卵巢CD 8aa+的谱系和表型，2）鉴定卵巢CD 8aa+细胞参与的卵巢功能，和3）鉴定TECK表达卵巢细胞并确定卵巢中TECK表达的激素调节来检验假设。