title: 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.
authors.affiliation: Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Lazaros I
authors.initials: LI
authors.lastname: Sakkas
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Carol M
authors.initials: CM
authors.lastname: Artlett
authors.forename: Song
authors.initials: S
authors.lastname: Lu
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Jimenez
authors.forename: Chris D
authors.initials: CD
authors.lastname: Platsoucas
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D003001:Cloning, Molecular; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D012867:Skin / Q000276:immunology* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*