Tumor Necrosis Factor-alpha Regulation of CD4+CD25+ T Cell Levels in NOD Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2002 Sep 11

PMID 12221281

Citations 86

Authors

Ava J Wu

Hong Hua

Sibyl H Munson

Hugh O McDevitt

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Development, Pre-Clinical Safety, and Immune Profile of RENOVAC-A Dimer RBD-Based Anti-Coronavirus Subunit Vaccine.

Muminov M, Tsiferova N, Pshenichnov E, Ermatova K, Charishnikova O, Abdullaev A Vaccines (Basel). 2025; 12(12.

PMID: 39772081 PMC: 11680381. DOI: 10.3390/vaccines12121420.

Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?.

Hardtke-Wolenski M, Landwehr-Kenzel S Mol Cell Pediatr. 2024; 11(1):3.

PMID: 38507159 PMC: 10954601. DOI: 10.1186/s40348-024-00176-8.

Interferons are key cytokines acting on pancreatic islets in type 1 diabetes.

Coomans de Brachene A, Alvelos M, Szymczak F, Zimath P, Castela A, Marmontel de Souza B Diabetologia. 2024; 67(5):908-927.

PMID: 38409439 DOI: 10.1007/s00125-024-06106-7.

Molecular mechanism of Hedyotis Diffusae Herba in the treatment of lupus nephritis based on network pharmacology.

Yang J, Li S Front Pharmacol. 2023; 14:1118804.

PMID: 37361229 PMC: 10285311. DOI: 10.3389/fphar.2023.1118804.

Regulatory T Cell Therapeutics for Neuroinflammatory Disorders.

Harkins A, Kopec A, Keeler A Crit Rev Immunol. 2023; 42(2):1-27.

PMID: 37017285 PMC: 11465901. DOI: 10.1615/CritRevImmunol.2022045080.

References

Pritchard N, Cutler A, Uribe S, Chadban S, Morley B, Smith K . Autoimmune-prone mice share a promoter haplotype associated with reduced expression and function of the Fc receptor FcgammaRII. Curr Biol. 2000; 10(4):227-30. DOI: 10.1016/s0960-9822(00)00344-4. View

Green E, Flavell R . Tumor necrosis factor-alpha and the progression of diabetes in non-obese diabetic mice. Immunol Rev. 1999; 169:11-22. DOI: 10.1111/j.1600-065x.1999.tb01302.x. View

Green E, Flavell R . The temporal importance of TNFalpha expression in the development of diabetes. Immunity. 2000; 12(5):459-69. DOI: 10.1016/s1074-7613(00)80198-3. View

Sakaguchi S . Regulatory T cells: key controllers of immunologic self-tolerance. Cell. 2000; 101(5):455-8. DOI: 10.1016/s0092-8674(00)80856-9. View

Read S, Malmstrom V, Powrie F . Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med. 2000; 192(2):295-302. PMC: 2193261. DOI: 10.1084/jem.192.2.295. View

Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N . Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med. 2000; 192(2):303-10. PMC: 2193248. DOI: 10.1084/jem.192.2.303. View

Nakashima T, Kobayashi Y, Yamasaki S, Kawakami A, Eguchi K, Sasaki H . Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun. 2000; 275(3):768-75. DOI: 10.1006/bbrc.2000.3379. View

Shevach E . Certified professionals: CD4(+)CD25(+) suppressor T cells. J Exp Med. 2001; 193(11):F41-6. PMC: 2193387. DOI: 10.1084/jem.193.11.f41. View

Christen U, Wolfe T, Mohrle U, Hughes A, Rodrigo E, Green E . A dual role for TNF-alpha in type 1 diabetes: islet-specific expression abrogates the ongoing autoimmune process when induced late but not early during pathogenesis. J Immunol. 2001; 166(12):7023-32. DOI: 10.4049/jimmunol.166.12.7023. View

10.

Kassiotis G, Kollias G . TNF and receptors in organ-specific autoimmune disease: multi-layered functioning mirrored in animal models. J Clin Invest. 2001; 107(12):1507-8. PMC: 200203. DOI: 10.1172/JCI13362. View

11.

Kukreja A, Cost G, Marker J, Zhang C, Sun Z, Lin-Su K . Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest. 2002; 109(1):131-40. PMC: 150819. DOI: 10.1172/JCI13605. View

12.

Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S . Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol. 2002; 3(2):135-42. DOI: 10.1038/ni759. View

13.

Green E, Choi Y, Flavell R . Pancreatic lymph node-derived CD4(+)CD25(+) Treg cells: highly potent regulators of diabetes that require TRANCE-RANK signals. Immunity. 2002; 16(2):183-91. DOI: 10.1016/s1074-7613(02)00279-0. View

14.

McHugh R, Whitters M, Piccirillo C, Young D, Shevach E, Collins M . CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity. 2002; 16(2):311-23. DOI: 10.1016/s1074-7613(02)00280-7. View

15.

Sheehan K, Ruddle N, Schreiber R . Generation and characterization of hamster monoclonal antibodies that neutralize murine tumor necrosis factors. J Immunol. 1989; 142(11):3884-93. View

16.

Jacob C, Aiso S, Michie S, McDevitt H, Acha-Orbea H . Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1. Proc Natl Acad Sci U S A. 1990; 87(3):968-72. PMC: 53391. DOI: 10.1073/pnas.87.3.968. View

17.

Nabarra B, Dardenne M, Bach J . Thymic reticulum of autoimmune mice. II: Ultrastructural studies of mice with lupus-like syndrome (NZB, BXSB, MRL/l). J Autoimmun. 1990; 3(1):25-36. DOI: 10.1016/0896-8411(90)90004-c. View

18.

Giroir B, Brown T, Beutler B . Constitutive synthesis of tumor necrosis factor in the thymus. Proc Natl Acad Sci U S A. 1992; 89(11):4864-8. PMC: 49188. DOI: 10.1073/pnas.89.11.4864. View

19.

Nabarra B, Andrianarison I . Thymus reticulum of autoimmune mice. 3. Ultrastructural study of NOD (non-obese diabetic) mouse thymus. Int J Exp Pathol. 1991; 72(3):275-87. PMC: 2001942. View

20.

Yang X, Tisch R, Singer S, Cao Z, Liblau R, Schreiber R . Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process. J Exp Med. 1994; 180(3):995-1004. PMC: 2191653. DOI: 10.1084/jem.180.3.995. View