Response to Il-6 allows differentiation between inducible and natural regulatory T cells: Lessons from Women with Reproductive Failure

ARRUVITO L, SOTELO AI, BILLORDO A, FAINBOIM L.

CLINICAL IMMUNOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2010 vol. 136 p. 432 - 441

1521-6616

We have previously shown a decreased frequency and function of Tregs in women suffering from recurrent spontaneous abortions (RSA). In the current study, we first investigated the expression of FOXP3 after T-cell activation. We observed that expression of FOXP3 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 assessed the role of IL-2 signaling through STAT5, which is known to be required for generation of inducible Tregs (iTregs). We demonstrated not only that TGF-beta and IL-2 were diminished but also that the IL-2-STAT-5 signaling axis was down regulated in RSA women. Finally, in addition to a limited FOXP3(+) cells expansion in vitro, iTregs from RSA women showed a strikingly lower suppressor activity.