Natural Killer cells expressing a progesterone receptor are susceptible to progesterone-induced apoptosis

LOURDES ARRUVITO; SEBASTIÁN GIULIANELLI; ANA C. FLORES; NATALIA PALADINO; MARCOS BARBOZA; CLAUDIA LANARI; LEONARDO FAINBOIM

JOURNAL OF IMMUNOLOGY

Año: 2008 vol. 180 p. 5746 - 5753

0022-1767

It has been proposed that progesterone (P4) induces the suppression of immune responses, particularly during pregnancy. However, knowledge about the mechanisms involved has remained largely elusive. We demonstrate here that peripheral blood natural killer (PBNK) cells express both classical progesterone receptor (PR) isoforms and are specifically affected by the actions of P4 through two apparently independent mechanisms. Progesterone induces caspase-dependent PBNK cell death, which is reversed by two different anti-progestins, ZK 98.299 and RU 486, supporting the involvement of classical PR. It was suggested that CD56bright CD16- Killer Ig-like Receptor (KIR) -   NK cells might represent precursors cells, which upon activation, acquire the features of a more mature NK subset expressing KIR receptors. The present study demonstrated that PR expression seemed to be restricted to more mature KIR+ PBNK cells. The expression of PR had a functional counterpart in the suppressive effect of P4 on IL-12-induced IFN-ã secretion. This cytokine suppression was mainly observed in KIR+ PBNK cells, without affecting the high secretion of IFN-g by CD56bright PBNK cells. The lack of PR expression on CD56bright KIR- PBNK cells provides an additional phenotypic marker to test the idea that they might represent the PBNK precursors selectively recruited into the endometrium where they differentiate to become the uterine NK cells. Additionally, these findings might be relevant to NK cell function in viral immunity, human reproduction, and tumor immunity.