A physiological role for inducible FOXP3(+) Treg cells. Lessons from women with reproductive failure.
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.
Arruvito
Lourdes
L
Immunogenetics Laboratory, José de San Martín Clinical Hospital, Buenos Aires, Argentina.
Sotelo
Ana I
AI
Billordo
Ariel
A
Fainboim
Leonardo
L
D000026:Abortion, Habitual / Q000276:immunology*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005498:Follicular Phase / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007519:Isoantigens / Q000008:administration & dosage; D007700:Kinetics; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508594:IL2 protein, human; C508600:IL6 protein, human; D007376:Interleukin-2; D015850:Interleukin-6; D007519:Isoantigens; D050799:STAT5 Transcription Factor; D016212:Transforming Growth Factor beta