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

Arthritis Rheum. 2007 Jun;56(6):1910-20. doi: 10.1002/art.22699.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • CD4 Antigens / metabolism
  • Case-Control Studies
  • Cell Count
  • Dermatitis, Atopic / metabolism
  • Dermatitis, Atopic / pathology
  • Eczema / metabolism
  • Eczema / pathology
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lupus Erythematosus, Cutaneous / immunology*
  • Lupus Erythematosus, Cutaneous / metabolism
  • Lupus Erythematosus, Cutaneous / pathology*
  • Male
  • Middle Aged
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology*

Substances

  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit