T-cell receptor repertoire of infiltrating T cells in lachrymal glands, salivary glands and kidneys from alymphoplasia (aly) mutant mice: A new model for Sjögren's syndrome

Abstract

Alymphoplasia (aly) mice are thought to provide a new model for systemic Sjögren's syndrome (SS), since they reveal remarkable infiltration of mononuclear cells into salivary glands, lachrymal glands and kidneys, and show histological findings similar to those in patients with SS. Cell transfer experiments demonstrate that T cells induce the infiltration of mononuclear cells into several tissues in aly mice. To analyse the pathogenesis of cell infiltration in various tissues, we examined T-cell receptor (TCR) Vβ usage of T cells in salivary glands, lachrymal glands and kidneys from aly mice, using family-polymerase chain reaction (PCR) and PCR-single-strand conformation polymorphism (SSCP) methods. The results of SSCP demonstrated that the infiltrating T cells in the three organs expanded clonally, suggesting that they proliferate by antigen-driven stimulation. Some TCR Vβ genes (Vβ1, 3, 6, 11, 12, 16) were commonly used in salivary glands, lachrymal glands and kidneys, while the Vβ7 gene was specifically expressed in kidneys. SSCP also showed that there were a few shared T-cell clones (Vβ3- and Vβ6-positive cells) among the three tissues. Indeed, sequence analysis of accumulated T cells showed that a conserved amino acid (leucine) at position 98 in the TCR Vβ complementary determining region (CDR) 3 was detected in all organs at high frequency (41-57%) and the amino acid sequence motif (LG) was specifically conserved at a frequency of 32% in the three organs. In conclusion, T cells that infiltrate into lachrymal glands, salivary glands and kidneys of aly mutant mice might recognize shared common epitopes in all three organs and a kidney-specific antigen.