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Functional defect of circulating regulatory CD4+ T cells in patients with Wegener's granulomatosis in remission.
Arthritis Rheum. 2007 Jun; 56(6):2080-91.AR

Abstract

OBJECTIVE

Accumulating data support the role of regulatory T cells, a subset of CD4+ T cells that expresses CD25(high) and the transcription factor forkhead box P3 (FoxP3), in controlling and preventing autoimmunity. In Wegener's granulomatosis (WG), an autoimmune vasculitis, up-regulation of CD25 on circulating CD4+ T cells has been observed, even in patients in remission. The objective of this study was to test whether the frequency and/or function of Treg cells from WG patients in remission are disturbed.

METHODS

Peripheral blood mononuclear cells were freshly isolated from 52 WG patients in remission and from 27 age- and sex-matched healthy control subjects. The proportion of circulating Treg cells was assessed by flow cytometry using CD4, CD25, FoxP3, and CD45RO markers. Anergy and suppressive function of CD25(high),CD4+ T cells were determined using polyclonal stimulants and coculture assay in 10 WG patients in remission and in 10 age- and sex-matched healthy controls.

RESULTS

In WG patients, a significant increase was observed in the percentage of circulating CD25(high),CD4+ and CD25(low),CD4+ T cells, whereas CD25-,CD4+ T cells were decreased, as compared with healthy controls. Among circulating CD4+ T cells, an expanded percentage of Treg cells (CD25(high),FoxP3+) with memory phenotype was present in WG patients. However, when the suppressive function of CD25(high),CD4+ T cells was tested, CD25(high),CD4+ T cells from WG patients showed diminished or absent suppression of responder T cell proliferation. The impaired suppression was not due to responder cell resistance (as shown by crisscross experiments with T cells from healthy controls) or altered survival of Treg cells.

CONCLUSION

These data indicate that WG patients in remission have an expanded proportion of Treg cells that are functionally defective. This observation may be relevant to the development and relapsing course of this autoimmune vasculitis.

Authors+Show Affiliations

University Medical Center Groningen, Groningen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17530650

Citation

Abdulahad, Wayel H., et al. "Functional Defect of Circulating Regulatory CD4+ T Cells in Patients With Wegener's Granulomatosis in Remission." Arthritis and Rheumatism, vol. 56, no. 6, 2007, pp. 2080-91.
Abdulahad WH, Stegeman CA, van der Geld YM, et al. Functional defect of circulating regulatory CD4+ T cells in patients with Wegener's granulomatosis in remission. Arthritis Rheum. 2007;56(6):2080-91.
Abdulahad, W. H., Stegeman, C. A., van der Geld, Y. M., Doornbos-van der Meer, B., Limburg, P. C., & Kallenberg, C. G. (2007). Functional defect of circulating regulatory CD4+ T cells in patients with Wegener's granulomatosis in remission. Arthritis and Rheumatism, 56(6), 2080-91.
Abdulahad WH, et al. Functional Defect of Circulating Regulatory CD4+ T Cells in Patients With Wegener's Granulomatosis in Remission. Arthritis Rheum. 2007;56(6):2080-91. PubMed PMID: 17530650.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional defect of circulating regulatory CD4+ T cells in patients with Wegener's granulomatosis in remission. AU - Abdulahad,Wayel H, AU - Stegeman,Coen A, AU - van der Geld,Ymke M, AU - Doornbos-van der Meer,Berber, AU - Limburg,Pieter C, AU - Kallenberg,Cees G M, PY - 2007/5/29/pubmed PY - 2007/7/21/medline PY - 2007/5/29/entrez SP - 2080 EP - 91 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 56 IS - 6 N2 - OBJECTIVE: Accumulating data support the role of regulatory T cells, a subset of CD4+ T cells that expresses CD25(high) and the transcription factor forkhead box P3 (FoxP3), in controlling and preventing autoimmunity. In Wegener's granulomatosis (WG), an autoimmune vasculitis, up-regulation of CD25 on circulating CD4+ T cells has been observed, even in patients in remission. The objective of this study was to test whether the frequency and/or function of Treg cells from WG patients in remission are disturbed. METHODS: Peripheral blood mononuclear cells were freshly isolated from 52 WG patients in remission and from 27 age- and sex-matched healthy control subjects. The proportion of circulating Treg cells was assessed by flow cytometry using CD4, CD25, FoxP3, and CD45RO markers. Anergy and suppressive function of CD25(high),CD4+ T cells were determined using polyclonal stimulants and coculture assay in 10 WG patients in remission and in 10 age- and sex-matched healthy controls. RESULTS: In WG patients, a significant increase was observed in the percentage of circulating CD25(high),CD4+ and CD25(low),CD4+ T cells, whereas CD25-,CD4+ T cells were decreased, as compared with healthy controls. Among circulating CD4+ T cells, an expanded percentage of Treg cells (CD25(high),FoxP3+) with memory phenotype was present in WG patients. However, when the suppressive function of CD25(high),CD4+ T cells was tested, CD25(high),CD4+ T cells from WG patients showed diminished or absent suppression of responder T cell proliferation. The impaired suppression was not due to responder cell resistance (as shown by crisscross experiments with T cells from healthy controls) or altered survival of Treg cells. CONCLUSION: These data indicate that WG patients in remission have an expanded proportion of Treg cells that are functionally defective. This observation may be relevant to the development and relapsing course of this autoimmune vasculitis. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/17530650/Functional_defect_of_circulating_regulatory_CD4+_T_cells_in_patients_with_Wegener's_granulomatosis_in_remission_ L2 - https://doi.org/10.1002/art.22692 DB - PRIME DP - Unbound Medicine ER -