CD8aa+ Cells and Ovarian Functions

描述(申请人提供)：在这项申请中，我们建议研究一种新的卵巢CD8aa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经被认识到。胸腺在卵巢功能中的关键作用是众所周知的。因此，裸鼠是不育的，胸腺切除会导致卵巢功能障碍。然而，目前仍不清楚胸腺如何参与卵巢功能。在人绒毛膜促性腺激素(HCG)诱导的排卵过程中，我们在有腔卵泡内部发现了一个新的CD8aa群体，并发现CD8aa大量流入排卵卵泡。这种新的CD8aa细胞可能起源于胸腺，参与重要的卵巢功能，如排卵。因此，将含有几个CD8aa细胞群的同基因胸腺细胞转移到雌性裸鼠体内，恢复了它们的排卵能力。接下来，我们发现卵巢中趋化因子Teck(胸腺表达的趋化因子)的表达对CD8aa细胞在排卵期间归巢和进入卵巢至关重要。因此，在雌性BALB/c小鼠中主动免疫诱导产生抗Teck抗体，不仅导致卵巢CD8aa细胞的减少，而且导致免疫小鼠不育。基于以上结果，我们推测了胸腺与卵巢功能之间的一种新的关系：1)新的CD8aa细胞起源于胸腺，并由卵巢TECK在激素调节下招募到卵巢中；2)CD8aa细胞对排卵/黄体生成起关键作用。这旨在通过1)确定卵巢CD8aa的谱系和表型，2)鉴定卵巢CD8aa细胞参与的卵巢功能，以及3)鉴定表达Teck的卵巢细胞和确定卵巢中Teck表达的激素调节来检验假说。

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.