Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice.
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.
Wu
Ava J
AJ
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hua
Hong
H
Munson
Sibyl H
SH
McDevitt
Hugh O
HO
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D017634:Self Tolerance; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha