Oligoclonal expansion of intraepidermal T cells in psoriasis skin lesions.
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.
Lin
W J
WJ
Gilead Sciences, Inc., Boulder, Colorado, USA. weijenlin@csupomona.edu
Norris
D A
DA
Achziger
M
M
Kotzin
B L
BL
Tomkinson
B
B
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000235:genetics; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics
D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta