Under the Influence

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Science  02 Jul 2004:
Vol. 305, Issue 5680, pp. 21
DOI: 10.1126/science.305.5680.21b

Autoimmune diseases such as type 1 diabetes are thought to occur, in part, because of a breakdown in the normal regulatory networks that operate among T cells. Although our understanding of regulatory T cell function is improving, how potentially autoaggressive T cells might be rendered responsive to this regulation is not completely clear.

Using a mouse model of type 1 diabetes, McGregor et al.examined the role of CD154 and its receptor CD40: a well-characterized pathway in T cell activation. Although transgenic coexpression of the inflammatory cytokine tumor necrosis factor and the T cell activation ligand CD80 in pancreatic islet cells rendered these mice susceptible to diabetes, onset of the disease was significantly hastened in the absence of CD154. This corresponded with a decline in the presence of T cells with a regulatory phenotype, as well as an impaired ability of disease-causing T cells to respond to regulatory signals. Indirectly, this suggests that the CD40 ligand expressed by autoaggressive T cells is required to sanction the acceptance of regulatory cues. — SJS

Proc. Natl. Acad. Sci. U.S.A. 101, 9345 (2004).

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