Accumulation of common T cell clonotypes in the salivary glands of patients with human T lymphotropic virus type I-associated and idiopathic Sjögren's syndrome.

Abstract

To clarify the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated Sjögren's syndrome (SS), the TCR Vbeta gene usage by the infiltrating lymphocytes in the target organ was examined. The Vbeta families predominantly used in the labial salivary gland (LSG) from the HTLV-I-seropositive (HTLV-I+) SS patients were more restricted than those from the HTLV-I-seronegative (idiopathic) SS patients, and were commonly Vbeta5.2, Vbeta6, and Vbeta7. The single-strand conformation polymorphism analysis revealed that T cell clonotypes with Vbeta5.2, Vbeta6, and Vbeta7 accumulate in the LSG from the HTLV-I+ and idiopathic SS patients. Among junctional sequences of the most dominant Vbeta7 transcripts, the conserved amino acid motif (QDXG: X is any amino acid) was found in six of the five HTLV-I+ SS patients and was also detected in two of the five idiopathic SS patients. Using the probes specific to the motif, the Vbeta7 transcripts with the motif were detected in the LSG from all of the seven HTLV-I+ and five of the six idiopathic SS patients, but not from eight healthy subjects. The Vbeta7 transcripts with this motif were also detected in the HTLV-I-infected T cell lines obtained from the LSG of an HTLV-I+ SS patient. The accumulation of HTLV-I-infected T cells expressing TCR with the conserved motif was thus indicated. These T cells were commonly present in patients with idiopathic SS and are strongly suggested to most likely be involved in the pathogenesis of both HTLV-I-associated and idiopathic SS.