EFFECTS OF ENDOMETRIAL SERPIN-LIKE PROTEINS ON IMMUNE-RESPONSES IN SHEEP

PROBLEM: The uterine milk proteins (UTMP) are a pair of related glycop roteins that are the major secretory products of the endometrium of th e pregnant ewe. UTMP are members of the serpin superfamily of serine p rotease inhibitors bur have no known antiprotease activity. One possib le role for UTMP is to inhibit uterine immune responses-UTMP inhibit m itogen and mixed lymphocyte-induced proliferation of peripheral blood lymphocytes, natural killer (NK) cell activity and abortion caused by NK cell activation. Present objectives were to further evaluate the ly mphocyte-inhibitory activity of UTMP and test whether UTMP modify immu ne responses in vivo. METHOD: One experiment demonstrated that UTMP in hibited antigen-induced lymphocyte proliferation induced by Candida al bicans extract. In another experiment, ewes were immunized with OVA mi xed with 3.75 mg/ml of UTMP or ovine serum albumin (OSA control). Inje ctions of 1 mg OVA + UTMP or OSA in incomplete adjuvant were administe red 6 wk later. Titers of antibody to OVA were lower (P<0.001) for ewe s administered UTMP than for ewes administered OSA. Effects of UTMP on delayed hypersensitivity reactions were evaluated in three experiment s using skin-fold thickness assays. RESULTS: UTMP did not inhibit the increase in skin-fold thickness caused by PHA and Mycobacterium tuberc ulosis but rather tended to increase the response to PHA. CONCLUSION: Results strengthen the thesis that UTMP are physiologically relevant i mmunoregulatory molecules. Nonetheless, effects on skin-fold responses indicate that actions of UTMP can be more complex than would be predi cted based on the proteins only having a single biological effect.