CD8aa+ Cells and Ovarian Functions

描述（由申请人提供）：在本申请中，我们提出研究一种新的卵巢CD8aa+细胞群如何参与卵巢重要功能，如排卵。免疫系统在卵巢功能中的作用已被确认。胸腺在卵巢功能中的关键作用是众所周知的。因此，无胸腺裸雌性小鼠是不育的，胸腺切除术导致卵巢功能障碍。然而，目前还不清楚胸腺是如何参与卵巢功能的。我们已经确定了一种新的CD8aa+群体在卵泡内部，并在hcg诱导的排卵过程中大量涌入排卵卵泡。这种新的CD8aa+细胞可能起源于胸腺，并参与重要的卵巢功能，如排卵。因此，将含有多个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，我们确定了趋化因子TECK（胸腺表达的趋化因子）的卵巢表达对于CD8aa+细胞在排卵期间归巢和流入卵巢至关重要。因此，在雌性BALB/c小鼠中通过主动免疫激发抗teck抗体，不仅导致卵巢CD8aa+细胞减少，而且导致免疫小鼠不孕。基于上述结果，我们假设胸腺与卵巢功能之间存在一种新的关系：1)新的CD8aa+细胞起源于胸腺，并通过卵巢TECK被募集到卵巢，受激素调节；2)CD8aa+细胞对排卵/黄体生成至关重要。本研究旨在通过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，3)鉴定表达TECK-的卵巢细胞和确定激素对卵巢TECK表达的调节来验证假设。

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.