Oligoclonal expansion of intraepidermal T cells in psoriasis skin lesions

J Invest Dermatol. 2001 Dec;117(6):1546-53. doi: 10.1046/j.0022-202x.2001.01548.x.

Abstract

CD8(+) T cell infiltration into the epidermis is thought to be a key event in the pathogenesis of psoriasis. A quantitative competitive polymerase chain reaction method was developed to examine the expression of T cell receptor beta chain variable region 2, 3, 6.1-3, 8, and 13.1 genes in the epidermis of psoriatic lesions. Paired epidermal samples and peripheral blood samples from five psoriasis patients were studied. The results demonstrated the expansion of T cell receptor beta chain variable region 3 (two patients), 8 (two patients), and/or 2 (one patient). Contrary to previous reports, neither beta chain variable region 6.1-3 nor beta chain variable region 13.1 subgroups were expanded in any of the lesions. DNA sequence analysis revealed dominant T cell clones observed in all expanded beta chain variable region families and heterogeneous populations and/or small clones observed in non-expanded beta chain variable region families. Using CDR3 length analysis to examine the complete beta chain repertoire of the infiltrating T cells in the lesional epidermis, we found that approximately 50% of the T cell receptor beta chain variable region families in each patient's lesion demonstrated abnormal CDR3 DNA length distribution, indicating the presence of monoclonal or oligoclonal T cell expansion. Together, the results show that among different patients, T cell oligoclonality is not restricted to a limited number of T cell receptor beta chain variable region families. In an attempt to identify the pathogenic T cells among the many expanded T cell clones in the lesions, we compared T cell receptor expansion in the lesional epidermis with non-lesional epidermis. Particular T cell receptor were found to be preferentially expanded in lesional epidermis and these lesion-specific T cell clones may be most important in the pathogenesis and development of psoriatic lesions.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Biopsy
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology*
  • Clone Cells
  • Complementarity Determining Regions / genetics
  • Epidermis / immunology
  • Epidermis / pathology
  • Female
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Psoriasis / immunology*
  • Psoriasis / pathology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics

Substances

  • Complementarity Determining Regions
  • Immunoglobulin Variable Region
  • Receptors, Antigen, T-Cell, alpha-beta