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Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140; and
Department of Medicine, Rheumatology Division, Thomas Jefferson University School of Medicine, Philadelphia, PA 19103
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,
-chain TCR
transcripts from T cells infiltrating the skin of five patients with
SSc of recent onset were amplified by either V
-specific PCR or
nonpalindromic adaptor PCR. The resulting PCR products were
subsequently cloned and sequenced. High proportions of identical
-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.
-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.
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