The Role of γ/δ T Cells in Progesterone-Mediated Immunomodulation During Pregnancy: A Review


Department of Microbiology, University Medical School of Pecs, H-7643 Pecs, Hungary.


PROBLEM: To determine if pregnancy is recognized by the immune system and if inadequate recognition of fetal antigens might result in failed pregnancy.

METHOD OF STUDY: Review of literature and current data.

RESULTS: In the decidua γ/δ TCR positive cells significantly increase in number. A subset of γ/δ T cells reacts with nonpolymorphic Class I or Class I like molecules. Trophoblast recognition is mediated by the Vγ1 subset which recognize a conserved mammalian sequence on the trophoblast. Almost all γ/δ T cells in the decidua are activated and use the Vδ1 chain, whereas the majority of human peripheral γ/δ lymphocytes expresses Vγ9/Vδ2 TCR. Peripheral γ/δ T cells of healthy pregnant women preferentially use VγVδ1 chains, on the other hand, those of recurrent aborters use the Vγ9Vδ2 combination. Signaling via the Vγ1.4Vδl receptor induces a Th2 type response, whereas activation of the lymphocytes via the Vγ9Vδ2 receptor results in increased IL-12 production and natural killer (NK) activity. In the presence of progesterone, activated lymphocytes synthesize the progesterone induced blocking factor (PIBF), which inhibits NK activity and exerts an anti abortive effect in vivo. Decidual CD56 + and γδ + cells are to a high extent the same population.

CONCLUSION: All decidual CD56 + cells express PIBF, thus it cannot be excluded that local production of this substance contributes to low decidual NK activity and thus to the success of the pregnancy.