Persistence of T-cell clones in psoriatic lesions.

BACKGROUND: We previously demonstrated a clonal dominance in the V beta 13.1 messages isolated from the lesional CD8+ T cells of psoriasis vulgaris, which suggested an interaction of V beta 13.1+ CD8+ T cells with skin antigens. OBJECTIVES: To determine whether the clonality observed accurately reflected a clonal population of infiltrating T cells or was skewed by an overabundance of messages from a small number of cells, and to extend our study of V beta gene usage by lesional CD8+ T cells to 9 new patients. DESIGN: Case study. SETTING: Patients were enrolled at the Psoriasis Research Institute in Palo Alto, Calif, and samples were analyzed at The Immune Response Corporation in Carlsbad, Calif. MAIN OUTCOME MEASURES: For the 2 previous patients, skin samples were sorted directly for V beta 13.1+ T cells, for which the T-cell receptors were sequenced. For the 9 new patients, CD8+ T cells were sorted and their T-cell receptor V beta gene usage measured using semiquantitative polymerase chain reaction with V beta-specific primers. RESULTS: The directly sorted V beta 13.1+ T cells exhibited clonal dominance in both patients. The dominant V beta 13.1 clone in each patient was the same as that found in the previous 2 biopsy specimens for which CD8+ T cells were sorted. Additionally, in 8 of the 9 new patients examined, we again found a preferential usage of V beta 3 and/or V beta 13.1 genes by the lesional CD8+ T cells. CONCLUSIONS: The clonality, which was found in the V beta messages of the sorted CD8+ T cells, accurately reflects the dominance of these clones in the infiltrating T cells. Moreover, the persistence in the same patient of the same clone for as long as 15 months and the overrepresentation of V beta 3 and/or V beta 13.1 in lesional CD8+ T cells in the new patients examined support the pathogenic role of T cells bearing these V betas.

CD8+ T cells in psoriatic lesions preferentially use T-cell receptor V beta 3 and/or V beta 13.1 genes.

Psoriasis is an inflammatory skin disorder characterized by epidermal keratinocyte hyperproliferation in association with a cellular infiltrate. There is evidence that activated T cells play a role in psoriatic plaque formation. We examined the T-cell receptor beta-chain variable gene segment (V beta) use of epidermal T cells in shave biopsies of psoriatic lesions. Our results show increased expression of V beta 3 and/or V beta 13.1 messages in the CD8+, but not CD4+, T cells in the lesions of a majority of patients studied. Sequence analysis of complementarity-determining region 3 (CDR3) of these two V beta genes from the skin demonstrated monoclonality or marked oligoclonality. A second biopsy from the same or different lesions, performed 3.5-8 months later in four patients, again revealed increased V beta 3 and/or V beta 13.1 expression and clonality. Moreover, in three of the four patients, the same V beta CDR3 rearrangement was found in both biopsies, although there was no V beta CDR3 homology between patients. In two patients in which V beta 3 and/or V beta 13.1 was not increased, an increase in V beta 17 gene use and clonality was found. The clonality of V beta sequence data indicates these cells are recruited and expanded in situ. The persistence of V beta 3-and/or V beta 13.1-bearing CD8+ T cells in lesions that did not undergo resolution suggests their role as effector cells rather than as regulatory cells.