Expression of TIM-3 and CD9 Molecules on Natural Killer Cells (NK) and T-Lymphocytes with NK Functions (NKT) in the Peripheral Blood at Different Trimesters of Physiological Pregnancy.

Natural killer cells (NKs) and T-lymphocytes with NK functions (NKTs) are the major effectors of the maternal immune tolerance to a semi-allogeneic fetus, which additionally fulfil a feto-trophic function during physiological pregnancy. Tim-3 (T-cell Ig and mucin domain-containing protein 3) and CD9 molecules play a critical role in the implementation of immunoregulatory and feto-trophic functions of NKs and NKTs, however, their expression in peripheral blood cells has not been studied. The aim of this work was to study Tim-3 and CD9 expression in peripheral blood NK and NKT subpopulations during physiological pregnancy. The object of the study was the peripheral blood of healthy women in the first and third trimesters of pregnancy. The control group included healthy non-pregnant women in the first phase of the menstrual cycle. Tim-3 and CD9 expression was analyzed by flow cytometry in regulatory CD16–CD56bright NKs and CD16–CD56+ NKTs, as well as cytotoxic NK CD16+CD56dim/– NKs and CD16+CD56+ NKTs. It was found that in the first trimester of pregnancy, the total number and ratio of regulatory and cytotoxic NKs and NKTs did not change. Tim-3 expression increased in all NK and NKT subpopulations, except for cytotoxic CD16+CD56dim NKs. CD9 expression increased in all NK subpopulations, but in NKTs, it was indistinguishable from that in non-pregnant women. At the same time, a direct correlation between CD9 and Tim-3 expressions was revealed in regulatory NKs and NKTs in the first trimester of pregnancy. In the third trimester, the number of regulatory CD16–CD56bright NKs increased, while that of cytotoxic CD16+CD56dim NKs and regulatory CD16–CD56+ NKTs decreased compared to non-pregnant women. The number of CD16+CD56– NKs did not change in the first and third trimesters of pregnancy. Tim-3 expression was upregulated in all NK and cytotoxic NKT subpopulations, while CD9 was only upregulated in regulatory NKs. Thus, Tim-3 and CD9 expressions in different NK and NKT subpopulations changed in the first and third trimesters, which may play an important role in the regulation of their phenotype and functions during pregnancy. [ABSTRACT FROM AUTHOR]