Foxp3 expression in CD4+ T cells of patients with systemic lupus erythematosus: a comparative phenotypic analysis.
OBJECTIVE
The forkhead family transcription factor Foxp3 currently represents the most specific marker molecule for CD4(+)CD25(+) T cells with suppressive/regulatory capacity (Treg) in the mouse. Recent studies in the human system, however, indicate that the expression of Foxp3 can be T cell activation dependent. This tempted us to evaluate the significance of Foxp3 expression under autoimmune conditions with chronic T cell activation in patients with systemic lupus erythematosus (SLE) as compared with healthy controls (HCs).


METHODS
Proportions of peripheral blood CD4(+)Foxp3(+) T cells and CD4(+)CD25(high) T cells were determined in patients with active and inactive SLE as compared with HC by flow cytometry. Comparative analysis of the percentage of CD4(+)Foxp3(+) T cells and of percentage of CD4(+)CD25(high) T cells with clinical disease activity and T cell activation marker molecule expression were performed. Finally, the induction of Foxp3 expression was analysed upon T cell activation in vitro.


RESULTS
Proportions of CD4(+)Foxp3(+) T cells were significantly increased in patients with SLE as compared with HC and a significant correlation was observed between clinical disease activity and proportions of CD4(+)Foxp3(+) T cells. On the other hand, proportions of CD4(+)CD25(high) were decreased in SLE and no correlation with a T cell activation marker expression of was observed. In addition, in vitro activation of T cells induced Foxp3 expression.


CONCLUSIONS
Our data suggest that the expression of Foxp3 on CD4(+) T cells in patients with SLE, at least to some extent, reflects the activation of CD4(+) T cells due to underlying disease activity and does not necessarily indicate a functional regulatory T cell capacity.
Bonelli
M
M
Division of Rheumatology, Internal Medicine III, Medical University of Vienna, General Hospital of Vienna, Austria.
von Dalwigk
K
K
Savitskaya
A
A
Smolen
J S
JS
Scheinecker
C
C
D000208:Acute Disease; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D037181:Lectins, C-Type; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D015854:Up-Regulation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C418974:FOXP3 protein, human