A physiological role for Inducible FOXP3+ Treg cells. Lessons from Women with Reproductive Failure

ARRUVITO LOURDES

Congreso; 1st Franco-Argentine Immunlogy Congress; 2010

A physiological role for Inducible FOXP3+ Treg cells. Lessons from Women with Reproductive Failure  Lourdes Arruvito,* Ana I Sotelo,† Ariel Billordo,* and Leonardo Fainboim* *Immunogenetics Laboratory, “José de San Martín” Clinical Hospital, School of Medicine, University of Buenos Aires. †Department of Biochemistry, School of Biochemistry, University of Buenos Aires, National Council for Scientific and Technological Research, Buenos Aires, Argentina   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 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 STAT-5, which is known to be required for generation of inducible Tregs (iTregs). We demonstrated not only that TGF-β and IL-2 were diminished but also that the IL-2-STAT-5 signaling axis was down regulated in RSA women. In addition to a limited FOXP3+ cells expansion in vitro, iTregs from RSA women showed a strikingly lower suppressor activity. Finally, those conditions in which iTregs may play a central role can be associated with the expansion of Tregs observed in the pre-implantation phase of the menstrual cycle and during pregnancy.