Effects of endometrial serpin-like proteins on immune responses in sheep.

Abstract

The uterine milk proteins (UTMP) are a pair of related glycoproteins that are the major secretory products of the endometrium of the pregnant ewe. UTMP are members of the serpin superfamily of serine protease inhibitors but have no known antiprotease activity. One possible role for UTMP is to inhibit uterine immune responses--UTMP inhibit mitogen 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 lymphocyte-inhibitory activity of UTMP and test whether UTMP modify immune responses in vivo. One experiment demonstrated that UTMP inhibited antigen-induced lymphocyte proliferation induced by Candida albicans extract. In another experiment, ewes were immunized with OVA mixed with 3.75 mg/ml of UTMP or ovine serum albumin (OSA control). Injections of 1 mg OVA+UTMP or OSA in incomplete adjuvant were administered 6 wk later. Titers of antibody to OVA were lower (P < 0.001) for ewes administered UTMP than for ewes administered OSA. Effects of UTMP on delayed hypersensitivity reactions were evaluated in three experiments using skin-fold thickness assays. UTMP did not inhibit the increase in skin-fold thickness caused by PHA and Mycobacterium tuberculosis but rather tended to increase the response to PHA. Results strengthen the thesis that UTMP are physiologically relevant immunoregulatory molecules. Nonetheless, effects on skin-fold responses indicate that actions of UTMP can be more complex than would be predicted based on the proteins only having a single biological effect.