Previous reports have suggested that regulatory T cells (Treg) are abnormal in patients with systemic lupus erythematosus (SLE). In the present work, we quantified CD4+FOXP3+ Treg cells in patients with SLE and found no quantitative alterations. However, we found a clear defect in suppression assays. Surprisingly, SLE-derived Treg cells exhibited a normal phenotype and functional capacity. Conversely, SLE-derived CD4+CD25− effector T cells resisted suppression by autologous and allogeneic regulatory cells. Our findings strongly suggest that the defect in T-cell suppression observed in SLE is because of effector cell resistance and not because of an abnormal regulatory function.
1 Sakaguchi S . Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses.Annu Rev Immunol2004; 22: 531 – 562 .
2.
2 Picca CCLarkin JBoesteanu ALerman MARankin ALCaton AJ . Role of TCR specificity in CD4+ CD25+ regulatory T-cell selection.Immunol Rev2006; 212: 74 – 85 .
3.
3 Nishikawa HKato TTawara I . Definition of target antigens for naturally occurring CD4+ CD25+ regulatory T cells.J Exp Med2005; 201: 681 – 686 .
4.
4 Shevach EM . Certified professionals: CD4+CD25+ suppressor T cells.J Exp Med2001; 193: 41 – 46 .
5.
5 Fontenot JDRasmussen JPWilliams LMDooley Farr AGRudensky AY . Regulatory T cell lineage specification by the forkhead transcription factor Foxp3.Immunity2005; 22: 329 – 341 .
6.
6 Hori SNomura TSakaguchi S . Control of regulatory T cell development by the transcription factor Foxp3.Science2003; 299: 1057 – 1061 .
7.
7 Owen CJJennings CEImrie H . Mutational analysis of the FOXP3 gene and evidence for genetic heterogeneity in the immunodysregulation, polyendocrinopathy, enteropathy syndrome.J Clin Endocrinol Metab2003; 88: 6034 – 6039 .
8.
8 Crispín JCMartínez AAlcocer-Varela J . Quantification of regulatory T cells in patients with systemic lupus erythematosus.J Autoimmunity2003; 3: 273 – 276 .
9.
9 Liu MFWang CRFung LLWu CR . Decreased CD4+CD25+ T cells in peripheral blood of patients with systemic lupus erythematosus.Scand J Immunol2004; 59: 198 – 202 .
10.
10 Miyara MAmoura ZParizot C . Global natural regulatory T cell depletion in active systemic lupus erythematosus.J Immunol2005; 175: 8392 – 8400 .
11.
11 Lee JHWang LCLin YTYang YHLin DTChiang BL . Inverse correlation between CD4+ regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus.Immunology2006; 117: 280 – 286 .
12.
12 Baecher-Allan CBrown JAFreeman GJHafler DA . CD4+CD25+ high regulatory cells in human peripheral blood.J Immunol2001; 167: 1245 – 1253 .
13.
13 Ehrenstein MREvans JGSingh A . Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy.J Exp Med2004; 200: 277 – 285 .
14.
14 Kriegel MALohman TGabler CBlank NKalden JRLorenz HM . Defective suppressor function of human CD4+CD25+ regulatory T cells in autoimmune polyglandular syndrome type II.J Exp Med2004; 199: 1285 – 1291 .
15.
15 Viglietta VBaecher-Allan CWeiner HLHafler DA . Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis.J Exp Med2004; 199: 971 – 979 .
16.
16 Balandina ALécart SDartevelle PSaoudi ABerrih-Aknin S . Functional defect of regulatory CD4+CD25+ T cells in the thymus of patients with autoimmune mysthenia gravis.Blood2005; 105: 735 – 741 .
17.
17 Monk CRSpachidou MRovis F . MRL/Mp CD4+CD25- T cells show reduced sensitivity to suppression by CD4+CD25+ regulatory T cells in vitro: a novel defect of T cell regulation in systemic lupus erythematosus.Arthritis Rheum2005; 52: 1180 – 1184 .
18.
18 Tan EMCohen ASFries JF . The 1982 revised criteria for the classification of systemic lupus erythematosus.Arthritis Rheum1982; 25: 1271 – 1277 .
19.
19 Guzmán JCardiel MHArce-Salinas ASánchez-Guerrero JAlarcón-Segovia D . Measurement of disease activity in systemic lupus erythematosus. Prospective validation of 3 clinical indices.J Rheumatol1992; 19: 1551 – 1558 .
20.
20 Hori STakahashi TSakaguchi S . Control of autoimmunity by naturally arising regulatory CD4+ T cells.Adv Immunol2003; 81: 331 – 371 .
21.
21 Sakaguchi SSakaguchi NItoh MToda M . Immunologic self-tolerance maintained by activated T cells expressing IL–2 receptor α-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.J Immunol1995; 155: 1151 – 1164 .
22.
22 Crispín JCMartínez Ade Pablo PVelasquillo CAlcocer-Varela J . Participation of the CD69 antigen in the T-Cell activation process of patients with systemic lupus erythematosus.Scand J Immunol1998; 48: 196 – 200 .
23.
23 Bonelli Mvon Dalwigk KSavitskaya ASmolen JSScheinecker C . Foxp3 espression in CD4+ T cells of patients with systemic lupus erythematosus (SLE): a comparative phenotypic analysis.Ann Rheum Dis, Aug 2007; doi: 10.1136/ard.2007.074690.
24.
24 Kyttaris VCTsokos GC . T lymphocytes in systemic lupus erythematosus: an update.Curr Opin Rheumatol2004; 16: 548 – 552 .
25.
25 Valencia XYarboro CIllei GLipsky PE . Deficient CD4+CD25 high T regulatory cells function in patient with active systemic lupus erythematosus.J Immunol2007; 178: 2579 – 2588 .
