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Original Article

Regulation of Lymphocyte Proliferation by Uterine Serpin: Interleukin-2 mRNA Production, CD25 Expression and Responsiveness to Interleukin-2

Department of Dairy and Poultry Sciences, University of Florida, Gainesville, Florida 32611–0920

During pregnancy, the endometrium of the ewe secretes large amounts of a progesterone-induced protein of the serpin superfamily of serine proteinase inhibitors called ovine uterine serpin (OvUS). This protein inhibits lymphocyte proliferation in response to concanavalin A (ConA), phytohemagglutinin (PHA), or mixed lymphocyte reaction. The purpose of these experiments was to characterize the mechanism by which OvUS inhibits lymphocyte proliferation. Ovine US caused dose-dependent inhibition of lymphocyte proliferation induced by phorbol myristol acetate (PMA), an activator of protein kinase C. The PHA-induced increase in CD25 expression was inhibited in peripheral blood mononuclear leukocytes (PBML) by OvUS. However, no effect of OvUS on Con A-induced expression of CD25 was observed. Further analysis using two-color flow cytometry revealed that OvUS inhibited ConA-induced expression of CD25 in -TCR^- cells but not -TCR⁺ cells. Stimulation of PBML for 14 hr with ConA resulted in an increase in steady state amounts of interleukin-2 (IL-2) mRNA that was not inhibited by OvUS. Ovine US was also inhibitory to lymphocyte proliferation induced by human IL-2. Results suggest that OvUS acts to inhibit lymphocyte proliferation by blocking the upregulation of the IL-2 receptor and inhibiting IL-2–mediated events. Lack of an effect of OvUS on ConA-stimulated CD25 expression in -TCR⁺ cells may reflect a different mechanism of activation of these cells or insensitivity to inhibition by OvUS.

This article has been cited by other articles:

				P. J. Hansen Regulation of immune cells in the uterus during pregnancy in ruminants J Anim Sci, March 1, 2007; 85(13_suppl): E30 - E31. [Abstract] [PDF]

				S. Tekin, M. B. Padua, A. M. Brad, M. L. Rhodes, and P. J. Hansen Expression and Properties of Recombinant Ovine Uterine Serpin Experimental Biology and Medicine, September 1, 2006; 231(8): 1313 - 1322. [Abstract] [Full Text] [PDF]