Regulation of lymphocyte proliferation by uterine serpin: interleukin-2 mRNA production, CD25 expression and responsiveness to interleukin-2.
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 gammadelta-TCR- cells but not gammadelta-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 gammadelta-TCR+ cells may reflect a different mechanism of activation of these cells or insensitivity to inhibition by OvUS.
Peltier
M R
MR
Department of Dairy, University of Florida, Gainesville, 32611, USA.
Liu
W J
WJ
Hansen
P J
PJ
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D015843:Serpins / Q000302:isolation & purification / Q000494:pharmacology*; D012756:Sheep; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects; D014599:Uterus / Q000276:immunology / Q000502:physiology*
D007376:Interleukin-2; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D015843:Serpins; D003208:Concanavalin A