Regulatory T Cells in Human Autoimmune Diseases

Overview

Journal Springer Semin Immunopathol

Specialty Allergy & Immunology

Date 2006 Aug 12

PMID 16902772

Citations 19

Authors

Troy R Torgerson

Affiliations

Soon will be listed here.

Abstract

In the most simplistic terms, immune tolerance can be envisioned as a balance with autoreactive cells that arise naturally in all individuals on one side and regulatory mechanisms designed to counter those autoreactive processes on the other. A tilt of the balance toward the autoreactive side, either by increasing the number or function of autoreactive cells or by diminishing regulatory mechanisms, is manifested as autoimmunity. In contrast, tilting of the balance toward increased regulation could conceivably cause immunodeficiency. Regulatory T cells (T(REG)), and particularly the naturally arising CD4(+)CD25(+) subset of T(REG) cells, provide a substantial component of the autoimmune counterbalance. The identification of forkhead box P3 (FOXP3) as a critical determinant of CD4(+)CD25(+) T(REG) development and function has provided new opportunities and generated expanded interest in studying the delicate balance between autoimmunity and regulatory mechanisms in human autoimmune diseases. Identification of both human and mouse syndromes in which FOXP3 is mutated, and consequently CD4(+)CD25(+) T(REG) cells are absent, has led to a rapid accumulation of knowledge regarding T(REG) development and function over the past 5 years. The recent development of antibody reagents to specifically identify CD4(+)CD25(+) T(REG) cells by their FOXP3 expression has provided new tools to identify these elusive cells and investigate their role in human disease. This review will focus on the current state of knowledge regarding the role of T(REG) in human autoimmune diseases and on specific human immunodeficiencies that provide interesting models of autoimmunity.

Citing Articles

The potential role of cell surface complement regulators and circulating CD4+ CD25+ T-cells in the development of autoimmune myasthenia gravis.

Hamdoon M, Fattouh M, Nasr El-Din A, Elnady H Electron Physician. 2016; 8(1):1718-26.

PMID: 26955441 PMC: 4768919. DOI: 10.19082/1718.

Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment.

Garetto S, Trovato A, Lleo A, Sala F, Martini E, Betz A Immunobiology. 2015; 220(8):1025-9.

PMID: 25770018 PMC: 4457006. DOI: 10.1016/j.imbio.2015.02.006.

Late-onset of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome (IPEX) with intractable diarrhea.

Zama D, Cocchi I, Masetti R, Specchia F, Alvisi P, Gambineri E Ital J Pediatr. 2014; 40:68.

PMID: 25326164 PMC: 4421998. DOI: 10.1186/s13052-014-0068-4.

T helper cell polarization in healthy people: implications for cardiovascular disease.

Olson N, Sallam R, Doyle M, Tracy R, Huber S J Cardiovasc Transl Res. 2013; 6(5):772-86.

PMID: 23921946 PMC: 3806306. DOI: 10.1007/s12265-013-9496-6.

Functional defect in regulatory T cells in myasthenia gravis.

Thiruppathi M, Rowin J, Jiang Q, Sheng J, Prabhakar B, Meriggioli M Ann N Y Acad Sci. 2012; 1274:68-76.

PMID: 23252899 PMC: 3531815. DOI: 10.1111/j.1749-6632.2012.06840.x.

References

De Kleer I, Wedderburn L, Taams L, Patel A, Varsani H, Klein M . CD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol. 2004; 172(10):6435-43. DOI: 10.4049/jimmunol.172.10.6435. View

Giliani S, Bonfim C, de Saint Basile G, Lanzi G, Brousse N, Koliski A . Omenn syndrome in an infant with IL7RA gene mutation. J Pediatr. 2006; 148(2):272-4. DOI: 10.1016/j.jpeds.2005.10.004. View

Rieux-Laucat F, Le Deist F, Fischer A . Autoimmune lymphoproliferative syndromes: genetic defects of apoptosis pathways. Cell Death Differ. 2003; 10(1):124-33. DOI: 10.1038/sj.cdd.4401190. View

Walker M, Kasprowicz D, Gersuk V, Benard A, Van Landeghen M, Buckner J . Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest. 2003; 112(9):1437-43. PMC: 228469. DOI: 10.1172/JCI19441. View

Mazzolari E, Forino C, Fontana M, DIppolito C, Lanfranchi A, Gambineri E . A new case of IPEX receiving bone marrow transplantation. Bone Marrow Transplant. 2005; 35(10):1033-4. DOI: 10.1038/sj.bmt.1704954. View

Bindl L, Torgerson T, Perroni L, Youssef N, Ochs H, Goulet O . Successful use of the new immune-suppressor sirolimus in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). J Pediatr. 2005; 147(2):256-9. DOI: 10.1016/j.jpeds.2005.04.017. View

Vogel A, Strassburg C, Obermayer-Straub P, Brabant G, Manns M . The genetic background of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and its autoimmune disease components. J Mol Med (Berl). 2002; 80(4):201-11. DOI: 10.1007/s00109-001-0306-2. View

Betterle C, Greggio N, Volpato M . Clinical review 93: Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1998; 83(4):1049-55. DOI: 10.1210/jcem.83.4.4682. View

Suri-Payer E, Amar A, Thornton A, Shevach E . CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J Immunol. 1998; 160(3):1212-8. View

10.

Bousvaros A, Leichtner A, Book L, Shigeoka A, Bilodeau J, Semeao E . Treatment of pediatric autoimmune enteropathy with tacrolimus (FK506). Gastroenterology. 1996; 111(1):237-43. DOI: 10.1053/gast.1996.v111.pm8698205. View

11.

Schwartz R . Natural regulatory T cells and self-tolerance. Nat Immunol. 2005; 6(4):327-30. DOI: 10.1038/ni1184. View

12.

Ochs H, Notarangelo L . Structure and function of the Wiskott-Aldrich syndrome protein. Curr Opin Hematol. 2005; 12(4):284-91. DOI: 10.1097/01.moh.0000168520.98990.19. View

13.

Heino M, Peterson P, Sillanpaa N, Guerin S, Wu L, Anderson G . RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur J Immunol. 2000; 30(7):1884-93. DOI: 10.1002/1521-4141(200007)30:7<1884::AID-IMMU1884>3.0.CO;2-P. View

14.

Longhi M, Ma Y, Bogdanos D, Cheeseman P, Mieli-Vergani G, Vergani D . Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease. J Hepatol. 2004; 41(1):31-7. DOI: 10.1016/j.jhep.2004.03.008. View

15.

Lan R, Cheng C, Lian Z, Tsuneyama K, Yang G, Moritoki Y . Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology. 2006; 43(4):729-37. DOI: 10.1002/hep.21123. View

16.

Wildin R, Ramsdell F, Peake J, Faravelli F, Casanova J, Buist N . X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001; 27(1):18-20. DOI: 10.1038/83707. View

17.

Longhi M, Hussain M, Mitry R, Arora S, Mieli-Vergani G, Vergani D . Functional study of CD4+CD25+ regulatory T cells in health and autoimmune hepatitis. J Immunol. 2006; 176(7):4484-91. DOI: 10.4049/jimmunol.176.7.4484. View

18.

Fontenot J, Gavin M, Rudensky A . Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003; 4(4):330-6. DOI: 10.1038/ni904. View

19.

Wildin R, Smyk-Pearson S, Filipovich A . Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet. 2002; 39(8):537-45. PMC: 1735203. DOI: 10.1136/jmg.39.8.537. View

20.

Furihata M, Sawada T, Okada T, Ishizuka M, Horie T, Takagi K . Total colectomy improves altered distribution of regulatory T cells in patients with ulcerative colitis. World J Surg. 2006; 30(4):590-7. DOI: 10.1007/s00268-005-0301-9. View