ABSTRACT
Objective There were some identical T cell clonotypes expanded and accumulated in different organs in aged diseased (NZB?NZW)F1 and MRL/lpr mice. The amino acid motifs in the third complementarity determining region (CDR3) from the T cell receptor (TCR) V? chain was analyzed to demonstrate the antigenic specificity of these identical clones. Methods The TCR V?6 gene in kidneys and brains from different individuals of aged diseased lupus mice were amplified by reverse transcriptase polymerase chain reaction (RT-PCR) respectively. The amino acid motifs in CDR3 loops of TCR V?6 chain were demonstrated by DNA cloning and DNA sequence analysis. The amino acid motifs from the identical T cell clones accumulated in different organs were identified by single-strand conformation polymorphism (SSCP). Results Some conserved amino acid motifs such as isoleucine (I) and aspartic acid (D) were observed in CDR3 loops of TCR V?6 from these identical T cell clones in different individuals of aged diseased (NZB?NZW)F1 mice. Likewise, I, glycine (G) and D or glutamic acid (E) were also found in MRL/lpr mice. Conclusion These identical T cell clones may recognize restricted T cell epitopes on autoantigens and are involved in specific immune responses in SLE.
ABSTRACT
Objective CD4+ T lymphocytes have been shown to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). To identify the commonly accumulated T cell clones and to investigate its role in murine lupus models, it was analyzed that the T cell clonality infiltrating in different tissues derived from (NZB?NZW)F1 as well as MRL/lpr mice. Methods The expressions of T cell receptor (TCR) V? gene were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) combined with single-strand conformation polymorphism (SSCP) study. The phenotype of T cells expanded in different organs was determined by magnetic cell sorting (MACS). Results RT-PCR and SSCP study of TCR V? chain demonstrated that there were some identical T cell clonotypes expanded and accumulated in different organs in aged diseased mice. Most of these identical clonotypes were CD4+ T cells in both of the two strains. In contrast, young mice exhibited little accumulation of common clone in different organs. The TCR V? usage of these identical clonotypes was limited in V?2, V?6, V?8.1, V?10, V?16, V?18 in MRL/lpr mice and V?6, V?7 in (NZB?NZW)F1 mice respectively. Conclusion The results suggest that activated and clonally expanded CD4+ T cells commonly accumulated in different tissues in aged murine lupus models. These CD4+ T cell clonotypes may be involved in specific immune responses of SLE, thus playing a pathogenic role in these lupus mice.