Phenotypic and functional analysis of CD4+ CD25- Foxp3+ T cells in patients with systemic lupus erythematosus.
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) that specialize in the suppression of immune responses might be critically involved in the pathogenesis of autoimmune diseases. Recent studies have described increased proportions of CD4(+)Foxp3(+) T cells that lacked expression of CD25 in systemic lupus erythematosus (SLE) patients but the suppressive capacity of these cells has not been analyzed so far. We therefore performed combined phenotypic and functional analyses of CD4(+)CD25(-)Foxp3(+) T cells in patients with autoimmune diseases and healthy controls (HC). Phenotypic analysis revealed increased proportions of CD4(+)CD25(-)Foxp3(+) T cells in SLE patients as compared with patients with systemic sclerosis, rheumatoid arthritis, (RA), or HC. In addition, increased proportions of CD4(+)CD25(-)Foxp3(+) T cells correlated with the clinical disease activity and the daily cortisone dose. According to phenotypic analysis, CD4(+)CD25(-)Foxp3(+) T cells resembled regulatory T cells rather than activated T cells. For functional analysis, a surrogate surface marker combination to substitute for intracellular Foxp3 was defined: CD4(+)CD25(-)CD127(-) T cells from SLE patients were isolated by FACS sorting and analyzed for their suppressive capacity in vitro. CD4(+)CD25(-)CD127(-) T cells, that contained up to 53% Foxp3(+) T cells, were found to suppress T cell proliferation but not IFN-gamma production in vitro. In summary, CD4(+)CD25(-)Foxp3(+) T cells phenotypically and to a certain extent also functionally resemble conventional Treg. Despite increased proportions, however, their selective functional defects might contribute to the failure of Treg to control autoimmune dysregulation in SLE patients.
Bonelli
Michael
M
Division of Rheumatology, Internal Medicine III, General Hospital of Vienna, Medical University of Vienna, Vienna, Austria.
Savitskaya
Anastasia
A
Steiner
Carl-Walter
CW
Rath
Eva
E
Smolen
Josef S
JS
Scheinecker
Clemens
C
D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit