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

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 (T-H): polarization of secretory machinery for dedicated help delivery. To address this question, we visualized by confocal microscopy different parameters of activation in T-H and Treg cells interacting simultaneously with individual antigen-presenting cells (APC). Our results show that, although productive TCR engagement in T-H/APC conjugates was unaffected by the presence of adjacent Treg, the reorientation of T-H secretory machinery toward APC was strongly inhibited. Blocking TGF-beta completely reverted Treg induced inhibition of T-H polarization. Our results identify a previously undescribed mechanism by which Treg inhibit effector T cells. TGF-beta produced by adjacent Treg interferes with polarization of T-H secretory machinery toward APC, thus affecting a crucial step of T-H-mediated amplification of the immune response.