Tumor necrosis factor-α regulation of CD4+C25+T cell levels in NOD mice
Open Access
- 9 September 2002
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 99 (19), 12287-12292
- https://doi.org/10.1073/pnas.172382999
Abstract
The mechanism by which tumor necrosis factor-α (TNF) differentially modulates type I diabetes mellitus in the nonobese diabetic (NOD) mouse is not well understood. CD4+CD25+ T cells have been implicated as mediators of self-tolerance. We show (i) NOD mice have a relative deficiency of CD4+CD25+ T cells in thymus and spleen; (ii) administration of TNF or anti-TNF to NOD mice can modulate levels of this population consistent with their observed differential age-dependent effects on diabetes in the NOD mouse; (iii) CD4+CD25+ T cells from NOD mice treated neonatally with TNF show compromised effector function in a transfer system, whereas those treated neonatally with anti-TNF show no alteration in ability to prevent diabetes; and (iv) repeated injection of CD4+CD25+ T cells into neonatal NOD mice delays diabetes onset for as long as supplementation occurred. These data suggest that alterations in the number and function of CD4+CD25+ T cells may be one mechanism by which TNF and anti-TNF modulate type I diabetes mellitus in NOD mice.Keywords
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