Progesterone stimulates the induction of human endometrial CD56+ lymphocytes in an in vitro culture system.

An unusual population of large granular lymphocytes (LGL) with the surface phenotype CD56(bright+)/CD16-/CD3- increases in the human endometrium during the late secretory phase and early pregnancy. To identify the factor(s) that induces CD56+ LGL in the human endometrium, we isolated endometrial leukocytes from nonpregnant human endometrium and investigated changes in CD56+ cells during culture with various factors. Isolated endometrial leukocyte-rich fraction and peripheral blood mononuclear cells were cultured for 6 days in the presence of progesterone, estradiol, PRL, or hCG, then nonadherent cells were collected and examined immunocytochemically. Endometrial leukocyte-rich fractions were composed of leukocytes and endometrial stromal cells, and 53.2 +/- 5.8% of them expressed CD45 antigen before culture. Therefore, leukocytes and endometrial stromal cells were cocultured in these endometrial leukocyte-rich fraction cultures. The percentage of CD56+ cells in endometrial leukocyte-rich fractions cultured with progesterone was significantly higher than that in fractions without progesterone. On the other hand, estradiol, PRL, and hCG did not significantly induce CD56+ cells in endometrial leukocyte-rich fractions. There was no significant difference in the percentage of CD56+ cells between peripheral blood mononuclear cell cultures with and without progesterone. These findings suggest that progesterone is an important factor for the in situ proliferation or differentiation of CD56+ LGL in human endometrium.