Admirable Self Restraint

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Science  22 Mar 2002:
Vol. 295, Issue 5563, pp. 2181
DOI: 10.1126/science.295.5563.2181a

Peripheral suppression of autoreactive lymphocytes has been attributed to a subset of specialized regulatory T cells. Under the influence of these T-reg cells, which are defined by coexpression of CD4+CD25+and a pattern of cytokine expression, organ-specific autoimmunity is inhibited.

By controlling tumor necrosis factor α (TNFα) expression in pancreatic islet cells, Green et al. were able to manipulate the advance of diabetes in a mouse model and to probe the function of T-reg cells. The onset of disease in mice whose TNFα expression was repressed during a critical period 21 to 25 days after birth was delayed in comparison to mice expressing TNFα constitutively. This delay coincided with an increase in CD4+CD25+ T cells within pancreatic lymph nodes and islets, and adoptive transfer experiments confirmed that these cells were highly efficient in protecting against the development of diabetes. The appearance of these T-reg cells required a signaling pathway containing TNF-related activation-induced cytokine (TRANCE) and receptor activator of NF-κB (RANK). Inhibition of this pathway blocked recruitment of T-reg cells, allowing the differentiation of autodestructive CD8+ cytotoxic T cells within the pancreas. — SJS

Immunity16, 183 (2002).

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