Home LiteratureArticle Details
PMID: 15807863 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CD4+ CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis.

Clinical and experimental immunology ·Vol. 140 ·No. 2 ·2005-05-00 ·Pages 360-7

Möttönen M, Heikkinen J, Mustonen L, Isomäki P, Luukkainen R, Lassila O

Abstract

CD4(+) CD25(+) regulatory T (T(reg)) cells play a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity. In the present study, we have explored the characteristics of CD4(+) CD25(+) T(reg) cells in patients with rheumatoid arthritis (RA). The frequency and phenotype of CD4(+) CD25(+) T cells in paired samples of synovial fluid (SF) and peripheral blood (PB) from patients with RA and PB from normal controls were analysed. An increased frequency of CD4+ cells T cells expressing CD25 was detected in SF compared to PB from patients with RA. No significant difference was observed in the numbers of CD4(+) CD25(+) T cells in PB from patients and controls. SF CD4(+) CD25(+) T cells expressed high levels of CTLA-4 (both surface and intracellular), GITR and OX40, as well as Foxp3 transcripts. Functionally, SF CD4(+) CD25(+) T cells were impaired in their proliferative responses and could suppress the proliferation of their CD4(+) CD25(-) counterparts. In conclusion, these data demonstrate that CD4(+) CD25(+) T(reg) cells, with the potential to regulate the function of effector T cells and antigen-presenting cells, accumulate in the synovium of patients with RA.

MeSH Terms
Adult Aged Aged, 80 and over Arthritis, Rheumatoid/immunology CD4-Positive T-Lymphocytes/immunology Cell Proliferation Cells, Cultured DNA-Binding Proteins/metabolism Female Forkhead Transcription Factors Humans Immune Tolerance Immunophenotyping Lymphocyte Activation/immunology Male Middle Aged Receptors, Interleukin-2/analysis Synovial Fluid/immunology T-Lymphocyte Subsets/immunology
Chemicals
DNA-Binding Proteins FOXP3 protein, human Forkhead Transcription Factors Receptors, Interleukin-2
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Möttönen M
Turku Graduate School of Biomedical Sciences, Turku, Finland. [email protected]
Heikkinen J
Mustonen L
Isomäki P
Luukkainen R
Lassila O
References (44)
44 references, click to expand
  1. CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells.
    Eur J Immunol. 2000 Jun;30(6):1538-43 PMID: 10898488
  2. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy.
    J Exp Med. 2004 Aug 2;200(3):277-85 PMID: 15280421
  3. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3.
    Nat Genet. 2001 Jan;27(1):20-1 PMID: 11137993
  4. Cytokine, activation marker, and chemokine receptor expression by individual CD4(+) memory T cells in rheumatoid arthritis synovium.
    Arthritis Res. 2000;2(5):415-23 PMID: 11056676
  5. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide.
    Nat Immunol. 2001 Apr;2(4):301-6 PMID: 11276200
  6. Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro.
    Eur J Immunol. 2001 Apr;31(4):1247-54 PMID: 11298351
  7. Differentiation of T regulatory cells by immature dendritic cells.
    J Exp Med. 2001 Jan 15;193(2):F5-9 PMID: 11208869
  8. Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood.
    J Exp Med. 2001 Jun 4;193(11):1285-94 PMID: 11390435
  9. Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood.
    J Exp Med. 2001 Jun 4;193(11):1303-10 PMID: 11390437
  10. CD4+CD25high regulatory cells in human peripheral blood.
    J Immunol. 2001 Aug 1;167(3):1245-53 PMID: 11466340
  11. Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells.
    Blood. 2001 Nov 1;98(9):2736-44 PMID: 11675346
  12. B cells and professional APCs recruit regulatory T cells via CCL4.
    Nat Immunol. 2001 Dec;2(12):1126-32 PMID: 11702067
  13. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance.
    Nat Immunol. 2002 Feb;3(2):135-42 PMID: 11812990
  14. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor.
    Immunity. 2002 Feb;16(2):311-23 PMID: 11869690
  15. Studies of T-cell activation in chronic inflammation.
    Arthritis Res. 2002;4 Suppl 3:S197-211 PMID: 12110140
  16. Escherichia coli heat-labile enterotoxin B subunit prevents autoimmune arthritis through induction of regulatory CD4+ T cells.
    Arthritis Rheum. 2002 Jun;46(6):1671-82 PMID: 12115200
  17. Human CD4(+)CD25(+) regulatory, contact-dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells [corrected].
    J Exp Med. 2002 Jul 15;196(2):247-53 PMID: 12119349
  18. Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells.
    J Exp Med. 2002 Jul 15;196(2):255-60 PMID: 12119350
  19. CTLA-4-Ig regulates tryptophan catabolism in vivo.
    Nat Immunol. 2002 Nov;3(11):1097-101 PMID: 12368911
  20. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells.
    J Exp Med. 2002 Nov 18;196(10):1335-46 PMID: 12438424
  21. Control of regulatory T cell development by the transcription factor Foxp3.
    Science. 2003 Feb 14;299(5609):1057-61 PMID: 12522256
  22. Control of immune responses by naturally arising CD4+ regulatory T cells that express toll-like receptors.
    J Exp Med. 2003 Feb 17;197(4):397-401 PMID: 12591898
  23. Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis.
    Eur J Immunol. 2003 Jan;33(1):215-23 PMID: 12594850
  24. Regulatory T cells under scrutiny.
    Nat Rev Immunol. 2003 Mar;3(3):189-98 PMID: 12658267
  25. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.
    Nat Immunol. 2003 Apr;4(4):330-6 PMID: 12612578
  26. An essential role for Scurfin in CD4+CD25+ T regulatory cells.
    Nat Immunol. 2003 Apr;4(4):337-42 PMID: 12612581
  27. CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis.
    Arthritis Rheum. 2003 May;48(5):1452-60 PMID: 12746920
  28. CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid.
    Arthritis Rheum. 2004 Sep;50(9):2775-85 PMID: 15457445
  29. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
    Arthritis Rheum. 1988 Mar;31(3):315-24 PMID: 3358796
  30. Phenotypic analysis of synovial tissue and peripheral blood lymphocytes isolated from patients with rheumatoid arthritis.
    Arthritis Rheum. 1988 Oct;31(10):1230-8 PMID: 3263133
  31. Reduction of synovial inflammation after anti-CD4 monoclonal antibody treatment in early rheumatoid arthritis.
    Arthritis Rheum. 1995 Oct;38(10):1457-65 PMID: 7575695
  32. Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity.
    Arthritis Rheum. 1997 Feb;40(2):217-25 PMID: 9041933
  33. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production.
    J Exp Med. 1998 Jul 20;188(2):287-96 PMID: 9670041
  34. Highly sensitive and specific fluorescence reverse transcription-PCR assay for the pseudogene-free detection of beta-actin transcripts as quantitative reference.
    Clin Chem. 1999 Feb;45(2):297-300 PMID: 9931059
  35. Evolving concepts of rheumatoid arthritis.
    Nature. 2003 May 15;423(6937):356-61 PMID: 12748655
  36. Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion.
    J Immunol. 2003 Aug 15;171(4):1652-5 PMID: 12902462
  37. Dynamics of suppressor T cells: in vivo veritas.
    J Exp Med. 2003 Sep 15;198(6):845-9 PMID: 12975452
  38. The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery.
    J Clin Invest. 2003 Nov;112(9):1310-2 PMID: 14597756
  39. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells.
    J Clin Invest. 2003 Nov;112(9):1437-43 PMID: 14597769
  40. Modulation of tryptophan catabolism by regulatory T cells.
    Nat Immunol. 2003 Dec;4(12):1206-12 PMID: 14578884
  41. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis.
    J Exp Med. 2004 Apr 5;199(7):971-9 PMID: 15067033
  42. Cutting edge: human CD4+CD25+ T cells restrain the maturation and antigen-presenting function of dendritic cells.
    J Immunol. 2004 Apr 15;172(8):4676-80 PMID: 15067041
  43. CD25brightCD4+ regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease.
    Arthritis Res Ther. 2004;6(4):R335-46 PMID: 15225369
  44. 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 Jul 17;192(2):295-302 PMID: 10899916
Article Info
Journal
Clinical and experimental immunology
Abbr.
Clin Exp Immunol
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2005.02754.x
Email
[email protected]
Published
2005-05-00
Pages
360-7
Language
English
Region
England
NLM ID
0057202
PMCID
PMC1809357
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1365-2249.2005.02754.x PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2