Tags

Type your tag names separated by a space and hit enter

Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells.
Arthritis Rheum. 2008 Mar; 58(3):801-12.AR

Abstract

OBJECTIVE

To explore whether there are extrinsic factors that impair the suppressive function of CD4+,CD25+ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE).

METHODS

We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4+,CD25+,FoxP3+ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real-time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon-alpha (IFNalpha) in supernatants from the function assays were determined with an IFN-stimulated response element-luciferase reporter assay.

RESULTS

The percentage of CD4+,CD25+, FoxP3+ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean +/- SEM 9.11 +/- 0.73% versus 4.78 +/- 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4+,CD25+ T cell subset from SLE patients as compared with controls. Antigen-presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4+,CD25+ Treg cells from SLE patients exhibited normal suppressive activity when cultured with APCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFNalpha derived from SLE patient APCs.

CONCLUSION

We suggest that blockade of Treg cell-mediated suppression by IFNalpha-producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease.

Authors+Show Affiliations

Joint Molecular Rheumatology Laboratory of Renji Hospital, Shanghai JiaoTong University School of Medicine and Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Shanghai, China.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

18311820

Citation

Yan, Bing, et al. "Dysfunctional CD4+,CD25+ Regulatory T Cells in Untreated Active Systemic Lupus Erythematosus Secondary to Interferon-alpha-producing Antigen-presenting Cells." Arthritis and Rheumatism, vol. 58, no. 3, 2008, pp. 801-12.
Yan B, Ye S, Chen G, et al. Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells. Arthritis Rheum. 2008;58(3):801-12.
Yan, B., Ye, S., Chen, G., Kuang, M., Shen, N., & Chen, S. (2008). Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells. Arthritis and Rheumatism, 58(3), 801-12. https://doi.org/10.1002/art.23268
Yan B, et al. Dysfunctional CD4+,CD25+ Regulatory T Cells in Untreated Active Systemic Lupus Erythematosus Secondary to Interferon-alpha-producing Antigen-presenting Cells. Arthritis Rheum. 2008;58(3):801-12. PubMed PMID: 18311820.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells. AU - Yan,Bing, AU - Ye,Shuang, AU - Chen,Guangjie, AU - Kuang,Miao, AU - Shen,Nan, AU - Chen,Shunle, PY - 2008/3/4/pubmed PY - 2008/4/29/medline PY - 2008/3/4/entrez SP - 801 EP - 12 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 58 IS - 3 N2 - OBJECTIVE: To explore whether there are extrinsic factors that impair the suppressive function of CD4+,CD25+ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE). METHODS: We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4+,CD25+,FoxP3+ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real-time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon-alpha (IFNalpha) in supernatants from the function assays were determined with an IFN-stimulated response element-luciferase reporter assay. RESULTS: The percentage of CD4+,CD25+, FoxP3+ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean +/- SEM 9.11 +/- 0.73% versus 4.78 +/- 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4+,CD25+ T cell subset from SLE patients as compared with controls. Antigen-presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4+,CD25+ Treg cells from SLE patients exhibited normal suppressive activity when cultured with APCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFNalpha derived from SLE patient APCs. CONCLUSION: We suggest that blockade of Treg cell-mediated suppression by IFNalpha-producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/18311820/Dysfunctional_CD4+CD25+_regulatory_T_cells_in_untreated_active_systemic_lupus_erythematosus_secondary_to_interferon_alpha_producing_antigen_presenting_cells_ L2 - https://doi.org/10.1002/art.23268 DB - PRIME DP - Unbound Medicine ER -