Dominant Lesional T Cell Receptor Rearrangements Persist in Relapsing Psoriasis but are Absent from Nonlesional Skin: Evidence for a Stable Antigen-Specific Pathogenic T Cell Response in Psoriasis Vulgaris

Abstract

In a previous study we reported that clonally expanded T cell receptor beta-chain rearrangements characterized the T cell receptor usage in skin lesions of psoriasis vulgaris and indicated antigen-specific T cell selection. To assess the relevance of clonal T cell expansion for disease progression, we now determined if select clonal T cell receptor rearrangements persisted over time and were present in nonlesional skin. Sequential biopsies were taken from psoriatic skin lesions of two patients. V-D-J junctional regions of T cell receptor beta-chain variable region gene families 2, 3, 6, 13S1, and BV17 were cloned and sequenced, as these particular BV gene families are preferentially selected in psoriatic skin lesions. The lesional T cell receptor rearrangements were compared with the T cell receptor usage in nonlesional skin and in blood. Several T cell receptor beta-chain rearrangements with high transcript frequency in the first lesional biopsy were again found in sequential lesional biopsies taken as much as 3 y later from psoriasis relapses. Only T cell receptor beta-chain rearrangements with low transcript abundance showed variability in that several clones appeared for the first time or disappeared. Although nonlesional skin also exhibited a restricted T cell receptor usage with clonal T cell receptor rearrangements, the T cell receptor usage in lesional and nonlesional skin differed nearly completely. The select lesional recurrence of identical T cell receptor rearrangements reveals that inflammation in psoriasis involves the same clonally expanded T cell populations and the same antigens over prolonged periods of time. It hereby suggests that specifically recruited and locally expanded T cell clones are permanently involved in psoriatic inflammation and may play a crucial part in disease perpetuation.