Analyses of antigen-specific T cells in systemic types of autoimmune disorders.

点击翻译按钮获取中文摘要

The involvement of antigen-specific T cells in the pathogenesis of systemic types of autoimmune disorders is still controversial. Essentially, activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Therefore, it is crucial to detect such T cells in order to know the contribution of antigen -specific immune responses in the diseases. However, the methods available to analyze T cell clonality are still limited. In this respect, we have established a novel method using a combination of reverse transcriptase-polymerase chain reaction of T cell receptor beta chain transcripts and single strand conformation polymorphism (SSCP). Using this method, the dynamic changes of T cell clonal responses during an antigenic stimulation could be monitored. Analyses of several autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus and their animal models, revealed the involvement of antigen specific T cell immune responses. Furthermore, taking advantage of the reproducible mobility of a band in SSCP gel, we are now able to compare identities of the accumulated T cell clones in different samples Without the need for nucleotide sequencing of each clone. Such information can thus elucidate the occurrence of uniform or stable immunological reactions in the patients and also suggests that these reactions play an important role in the pathogenesis. Developing this system, we are also establishing a new strategy to determine the antigen specificities of these in vivo accumulating T cell clones.