Immunology

A Signal for Suppression

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Science  25 Mar 2005:
Vol. 307, Issue 5717, pp. 1841
DOI: 10.1126/science.307.5717.1841d

T cells with a dedicated regulatory function (T-reg) maintain a crucial balance in immune responses and prevent autoimmune responses by effector T cells. Although the cytokine transforming growth factor-β (TGF-β) is central to T-reg cell activity, key questions remain about how T-reg cells use this mediator.

Fahlén et al. explored the role of TGF-β using a model of colitis, in which pathogenic T cells induce severe intestinal inflammation after transfer to healthy lymphocyte-deficient mice; the inflammatory response can be suppressed if T-reg cells are cotransferred. In animals that received pathogenic T cells expressing a nonfunctional TGF-β receptor, T-reg cells were unable to prevent colitis, demonstrating that pathogenic effector T cells must receive TGF-β signals directly. However, the critical source of TGF-β appeared not to be the T-reg cells themselves, indicating that TGF-β is furnished by a distinct population of cells and that the role of T-reg cells is to provide an unidentified signal that acts in conjunction with TGF-β. Furthermore, in the absence of TGF-β, T-reg cells developed normally and retained the ability to suppress effector T cells. These results address the function and source of TGF-β in T-reg cell activity and point to unexplored pathways involved in mediating regulatory events. — SJS

J. Exp. Med. 201, 737 (2005).

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