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Human regulatory T cells inhibit polarization of T helper cells toward antigen-presenting cells via a TGF-β-dependent mechanism

Esquerré, Michael, Tauzin, Baptiste, Guiraud, Martine, Müller, Sabina, Saoudi, Abdelhadi, Valitutti, Salvatore
Proceedings of the National Academy of Sciences of the United States of America 2008 v.105 no.7 pp. 2550-2555
CD4-positive T-lymphocytes, adaptive immunity, antigen-presenting cells, confocal microscopy, humans, immune response, transforming growth factor beta
The molecular mechanisms used by regulatory T cells (Treg) to inhibit the effector phase of adaptive immune responses are still elusive. In the present work, we investigated the possibility that Treg may interfere with a basic biological function of T helper cells (TH): polarization of secretory machinery for dedicated help delivery. To address this question, we visualized by confocal microscopy different parameters of activation in TH and Treg cells interacting simultaneously with individual antigen-presenting cells (APC). Our results show that, although productive TCR engagement in TH/APC conjugates was unaffected by the presence of adjacent Treg, the reorientation of TH secretory machinery toward APC was strongly inhibited. Blocking TGF-β completely reverted Treg induced inhibition of TH polarization. Our results identify a previously undescribed mechanism by which Treg inhibit effector T cells. TGF-β produced by adjacent Treg interferes with polarization of TH secretory machinery toward APC, thus affecting a crucial step of TH-mediated amplification of the immune response.