Oligoclonal T Cell Expansion in the Skin of Patients with Systemic Sclerosis

Abstract

Fibrosis, microvascular fibroproliferative alterations, and autoantibody production are the main features of systemic sclerosis (SSc), and all of them can be explained by cytokine production by activated T cells. However, little is known about the role of T cells in the pathogenesis of SSc, and there is no information on the Ag(s) that elicits such activation. To determine whether T cells infiltrating the skin biopsies of patients with SSc are oligoclonal, beta-chain TCR transcripts from T cells infiltrating the skin of five patients with SSc of recent onset were amplified by either Vbeta-specific PCR or nonpalindromic adaptor PCR. The resulting PCR products were subsequently cloned and sequenced. High proportions of identical beta-chain TCR transcripts ranging from 43 to 90% of those sequenced were found in five patients, strongly suggesting the presence of oligoclonal T cells in these infiltrates. A dominant T cell clone was found to be clonally expanded in skin biopsies obtained from a single patient with SSc at three different times (0, 8, and 13 mo earlier) and from three different skin regions. beta-chain TCR transcripts from PBMC from normal donors (methodological control) were unique when compared with each other, typical for polyclonal populations of T cells. The finding of oligoclonal T cells infiltrating the skin of patients with SSc suggests that these T cells have undergone proliferation in situ in the skin and clonal expansion in response to as yet unidentified Ag(s). These results suggest that T cells are involved in the pathogenesis of the disease.