Gamma-delta TCR+ T-cells in systemic sclerosis (135.37)

Abstract

T-cell involvement may be central to the pathogenesis of systemic sclerosis (SSc). Like αβ TCR+ T-cells, γδ TCR+ T-cell diversity during T-cell development results in a repertoire of different T-cells each with a unique TCR. Therefore the probability of finding identical TCR on defined T-cell populations is negligible, except in the context of an antigen-driven T-cell response. To determine whether γδ TCR+ T-cells are clonally expanded in skin biopsies and/or peripheral blood of patients with SSc (n=7), γ-chain (VγI & Vγ9) and δ-chain (Vδ1 & Vδ2) TCR transcripts were amplified by gene-specific PCR, followed by cloning and sequencing. We report the presence of substantial proportions of identical VγI-chain transcripts (14.3%-37.2%; p<0.05), and Vγ9 transcripts (24%-83.3%; p<0.05) in skin biopsies and/or PBMC of patients with SSc. Likewise, there were multiple identical Vδ1-chain transcripts (25%-50%; p<0.05), and Vδ2-chain transcripts (18.1%-80%; p<0.05) in the samples analyzed. Extensive clonal expansions of γ- and δ-chain TCR transcripts were identified in skin biopsies and peripheral blood of patients with SSc, demonstrating the presence of oligoclonal populations of γδ TCR+ T-cells in these patients. These γδ TCR+ T-cells may have undergone activation and clonal expansion in vivo in response to as yet unidentified antigens. Future studies to identify the antigens recognized by these clonally expanded γδ TCRs will facilitate better understanding of SSc pathogenesis.