Human regulatory T cells inhibit polarization of T helper cells toward antigen-presenting cells via a TGF-beta-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.
Esquerré
Michael
M
Institut National de la Santé et de la Recherche Médicale, U563, Centre de Physiopathologie de Toulouse Purpan, Section Dynamique Moléculaire des Interactions Lymphocytaires, F-31300 Toulouse, France.
Tauzin
Baptiste
B
Guiraud
Martine
M
Müller
Sabina
S
Saoudi
Abdelhadi
A
Valitutti
Salvatore
S
D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D016764:Cell Polarity / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D002118:Calcium