Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 19; pp. 12287 - 12292
• Main Authors: Wu, Ava J, Hua, Hong, Munson, Sibyl H, McDevitt, Hugh O
• Format: Journal Article
• Language: English
• Published: United States 17-09-2002
• Subjects: Adoptive Transfer; Animals; Animals, Newborn; Antibodies, Monoclonal - administration & dosage; Autoimmunity; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - prevention & control; Female; Mice; Mice, Inbred NOD; Mice, Inbred Strains; Receptors, Interleukin-2 - metabolism; Self Tolerance; Spleen - immunology; Spleen - pathology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; Thymus Gland - immunology; Thymus Gland - pathology; Time Factors; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0027-8424

The mechanism by which tumor necrosis factor-alpha (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.