PROGESTERONE-INDUCED SECRETION OF DIPEPTIDYL PEPTIDASE-IV (CLUSTER DIFFERENTIATION ANTIGEN-26) BY THE UTERINE ENDOMETRIUM OF THE EWE AND COW THAT COSTIMULATES LYMPHOCYTE-PROLIFERATION

Dipeptidyl peptidase-IV(DPPIV) is a serine proteinase widely distribut ed in mammalian tissues, including lymphocytes, where it is identical to the T-cell activation antigen, cluster differentiation antigen-as. In the present study, DPPIV enzymatic activity was found in uterine se cretions of unilaterally pregnant ewes in increasing amounts as gestat ion progressed. Progesterone increased DPPIV in uterine secretions fro m ovariectomized ewes and cows. DPPIV was enriched from ovine uterine secretions by a combination of cation exchange, gel filtration, lectin , and Gly-Pro-NH2 affinity chromatographies. The mol wt was 107 kiloda ltons, as indicated by sodium dodecyl sulfate-polyacrylamide gel elect rophoresis under reducing conditions, and 140 kilodaltons by gel filtr ation. The pi was estimated to be 6.8. Enzymatic activity had a pH opt imum of 8.3 and a K-m,of 0.32 mM. The sequence of the 34 N-terminal am ino acids was 77-87% homologous to an internal region of human cluster differentiation antigen-26 and rat liver DPPIV. Thus, uterine DPPIV a ppears to be missing the signal sequence that allows integration into the cytoplasmic membrane. DPPIV was localized immunohistochemically to lumenal and glandular endometrial epithelial cells and, in some pregn ant ewes, discrete endometrial stromal cells. Highly enriched sheep ut erine DPPIV costimulated proliferation of mitogen-treated sheep lympho cytes. Stimulation occurred in the presence of the uterine milk protei ns, a pair of progesterone-induced endometrial secretory proteins with well characterized lymphocyte inhibitory activity. However, uterine m ilk proteins did not inhibit the costimulatory effect of DPPIV on phyt ohemagglutinin-L stimulated-lymphocyte proliferation. In conclusion, t he uterine endometrium synthesizes a biologically active form of DPPIV under the influence of progesterone that is capable of enhancing mito gen-stimulated T-lymphocyte proliferation.