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 distributed in mammalian tissues, including lymphocytes, where it is identical to the T-cell activation antigen, cluster differentiation antigen-26. In the present study, DPPIV enzymatic activity was found in uterine secretions of unilaterally pregnant ewes in increasing amounts as gestation progressed. Progesterone increased DPPIV in uterine secretions from 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 kilodaltons, as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, and 140 kilodaltons by gel filtration. The pI was estimated to be 6.8. Enzymatic activity had a pH optimum of 8.3 and a Km of 0.32 mM. The sequence of the 34 N-terminal amino acids was 77-87% homologous to an internal region of human cluster differentiation antigen-26 and rat liver DPPIV. Thus, uterine DPPIV appears 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 pregnant ewes, discrete endometrial stromal cells. Highly enriched sheep uterine DPPIV costimulated proliferation of mitogen-treated sheep lymphocytes. Stimulation occurred in the presence of the uterine milk proteins, a pair of progesterone-induced endometrial secretory proteins with well characterized lymphocyte inhibitory activity. However, uterine milk proteins did not inhibit the costimulatory effect of DPPIV on phytohemagglutinin-L stimulated-lymphocyte proliferation. In conclusion, the uterine endometrium synthesizes a biologically active form of DPPIV under the influence of progesterone that is capable of enhancing mitogen-stimulated T-lymphocyte proliferation.