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.
