A physiological role for inducible FOXP3+ TREG cellsB Lessons from women with reproductive failure

ARRUVITO LOURDES; SOTELO AI; BILLORDO ARIEL ; FAINBOIM LEONARDO

CLINICAL IMMUNOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2010 vol. 136 p. 432 - 441

1521-6616

Abstract We have previously shown a decreased frequency and function of Tregs in womensuffering from recurrent spontaneous abortions (RSA). In the current study, we firstinvestigated the expression of FOXP3 after T-cell activation. We observed that expression ofFOXP3 in activated PBMCs was already present above baseline before any cell division,indicating that it was induced in cells that were previously negative for this transcription factor.Because RSA women showed a more limited expansion of FOXP3-positive cells, we next assessedthe role of IL-2 signaling through STAT5, which is known to be required for generation ofinducible Tregs (iTregs). We demonstrated not only that TGF-β and IL-2 were diminished butalso that the IL-2?STAT-5 signaling axis was down regulated in RSA women. Finally, in additionto a limited FOXP3+ cells expansion in vitro, iTregs from RSA women showed a strikingly lowersuppressor activity.