期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 26, 页码 11918-11923出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1001749107
关键词
indoleamine 2,3-dioxygenase; regulatory T cells; tolerance in pregnancy; transforming growth factor beta
资金
- Associazione Italiana per la Ricerca sul Cancro
- Fondazione Cassa di Risparmio di Genova (CARIGE) [2006.1051-53]
- Ministero dell'Istruzione, dell'Universita e della Ricerca-Fondo per gli Investimenti della Ricerca di Base [RBLA039LSF]
- Progetti di Ricerca di Interesse Nazionale [20077NFBH8_005]
- Ministero del Lavoro, della Salute e delle Politiche Socali [2006-08]
- Agreement Ricerca Oncologica (RO) [3/07, 8/07]
- Ministero della Salute, Progetto Strategico [RFPS-2007-4-633146]
- Fondazione Italiana per la Ricerca sul Cancro
Regulatory T cells (Tregs) are thought to play a major role in pregnancy by inhibiting the maternal immune system and preventing fetal rejection. In decidual tissues, NK cells (dNK) reside in close contact with particular myelomonocytic CD14(+)(dCD14(+)) cells. Here we show that the interaction between dNK and dCD14(+) cells results in induction of Tregs. The interaction is mediated by soluble factors as shown by transwell experiments, and the prominent role of IFN-gamma is revealed by the effect of a neutralizing monoclonal antibody. Following interaction with dNK cells, dCD14(+) cells express indoleamine 2,3-dioxygenase (IDO), which, in turn, induces Tregs. Notably, unlike peripheral blood NK (pNK) cells, dNK cells are resistant to inhibition by the IDO metabolite L-kynurenine. Conditioned dCD14(+) cells also may induce Tregs through transforming growth factor-beta (TGF-beta) production or CTLA-4-mediated interactions, as indicated by the effect of specific neutralizing Abs. Remarkably, only the interaction between dNK and dCD14(+) cells results in Treg induction, whereas other coculture combinations involving either NK or CD14(+) cells isolated from peripheral blood are ineffective. Our study provides interesting clues to understanding how the crosstalk between decidual NK and CD14(+) cells may initiate a process that leads to Treg induction and immunosuppression. Along this line, it is conceivable that an impaired function of these cells may result in pregnancy failure.
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