CD8+ T cells in psoriatic lesions preferentially use T-cell receptor V(β)3 and/or V(β)13.1 genes

Abstract

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 β-chain variable gene segment (V(β)) use of epidermal T cells in shave biopsies of psoriatic lesions. Our results show increased expression of V(β)3 and/or V(β)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(β) 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(β)3 and/or V(β)13.1 expression and clonality. Moreover, in three of the four patients, the same V(β) CDR3 rearrangement was found in both biopsies, although there was no V(β) CDR3 homology between patients. In two patients in which V(β)3 and/or V(β)13.1 was not increased, an increase in V(β)17 gene use and clonality was found. The clonality of V(β) sequence data indicates these cells are recruited and expanded in situ. The persistence of V(β)3- and/or V(β)13.1-bearing CD8+ T cells in lesions that did not undergo resolution suggests their role as effector cells rather than as regulatory cells.