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Potential Roles of a Special CD8⁺ Cell Population and CC Chemokine Thymus-Expressed Chemokine in Ovulation Related Inflammation¹

Cindy Zhou^*, Jean Wu^*, Jason Borillo^*, Lisa Torres^*, John McMahon and Ya-Huan Lou^2,*

^* Department of Diagnostic Sciences DB, and Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center, Houston, TX 77030

It is well known that ovulation may be an inflammatory process. However, it remains elusive how immune cells participate in this process. We have identified a novel CD8⁺ population, which resembles tissue dendritic cells, in the theca of antral follicles. We further observed a dramatic influx of the CD8⁺cells into the ovulating follicles. This CD8⁺population was absent in the ovary of estradiol-induced anovulatory C31F₁ mice and subfertile athymic nude mice. Expression of a CC chemokine thymus-expressed chemokine (TECK) has previously been found in the ovary; we further demonstrated that TECK attracted CD8⁺cells into the ovary. Anti-TECK Ab, elicited in the female mice by active immunization, depleted the ovarian CD8⁺ cells in vivo. Mice with a high titer of TECK Ab failed to ovulate after superovulation induction. More importantly, the immunized mice had greatly reduced fertility, which was positively correlated with the Ab titers. Ovarian TECK expression was normal in anovulatory C31F₁ mice, suggesting that infertility in the immunized mice is due to a block of CD8⁺ cell migration. Finally, the origin of ovarian CD8⁺ cells was explored. Upon being transferred, thymic CD8⁺ cells were able to home to the theca of follicles in the recipients. Thus, ovarian CD8⁺ cells, which participate in the ovulation-related inflammation, may originate in the thymus.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by National Institutes of Health Grants R01 HD049613 and HD35993 (to Y.H.L.). C.Z. was supported by NIH T32HD07324, and Lisa Torres is supported by NIH R01DK60029-03S (to Y.H.L.) Under-represented Minority Supplement.

² Address correspondence and reprint requests to Dr. Ya-Huan Lou, Department of Diagnostic Sciences, DB, University of Texas Health Science Center at Houston, Houston, TX 77030. E-mail address: Yahuan.Lou{at}uth.tmc.edu

³ Abbreviations used in this paper: TECK, thymus expressed chemokine; DAPI, 4'-6-diamidino-2-phenylindole; hCG, human chorionic gonadotropin; PMSG, pregnant mare’s serum gonadotropin; rmTECK, recombinant mouse TECK; PFA, paraformaldehyde; E2, estradiol.