Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus

Objective. To define the phenotype and function of CD4+,CD25+ regulatory T cells (Treg) in patients with cutaneous lupus erythematosus (CLE), a heterogeneous autoimmune disease characterized primarily by inflammatory skin lesions. Methods. The number of Treg in skin specimens obtained from patients with various subtypes of CLE was investigated by immunohistochemical analysis, using anti-Foxp3 and anti-CD4 monoclonal antibodies. Furthermore, characterization of peripheral blood CD4+,CD25+ Treg from normal healthy donors and patients with CLE was carried out by flow cytometry, analyzing the expression of Foxp3 and Treg subpopulations. We also purified CD4+,CD25(high) Treg obtained from patients with CLE and tested the sensitivity of these cells to CD95L-mediated apoptosis. Results. Quantitative analysis of CD4+ T cells in skin lesions from patients with CLE revealed that the number was similar to that in lesions from patients with other chronic inflammatory diseases, but the number of Foxp3+ Treg in CLE was significantly reduced. There was no correlation between disease subtype and the frequency of Foxp3+ Treg in the skin of patients with CLE. In peripheral blood, no significant differences were observed in the number and phenotype of CD4+,CD25+ Treg or in the sensitivity to apoptosis of CD4+,CD25(high) Treg derived from patients with CLE and those derived from normal healthy donors. Conclusion. These data suggest that an organ-specific abnormality of Treg in the skin underscores the importance of analyzing Treg in the affected tissue. Such a local process might give insight into the pathogenic mechanisms of CLE and differs from a global peripheral dysfunction as reported for patients with a systemic manifestation of the disease.