Molecular analysis of the abnormal T cell function as a pathogenesis of autoimmune diseases

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To clarify the mechanism of abnormal T cell functions in various autoimmune diseases, we have explored the nature of human suppressor T cells in several aspects. We have utilized the culture system with immobilized mAb to CD3 molecular complex, in which B cells are very potently activated through direct interactions with stimulated T cells. We have obtained the following results. First, we have demonstrated that the suppression of B cell differentiation by human suppressor T cells requires the direct interactions between ICM-1 on activated B cells and LFA-1 on suppressor T cells. Second, we have revealed that the expression of DNA polymerase alpha in B cells is inhibited by human suppressor T cells in a reversible fashion.Finally, we have disclosed that anti-CD3 activated CD4+ T cells as well as CD8+ T cells irrespective of their expression of CD45RA molecule are able to stimulate resting B cells to express IL-2 receptor (CD25), at the same time when they suppress the maturation of previously activated B cells, indicating that human activated T cells can simultaneously provide help as well as suppression irrespective of their phenotypes. It is rather suggested that the state of activation of B cells might be important in determining of functions of the activated T cells.All of these results have added novel findings to the body of knowledge about human suppressor T cells, and thus may contribute to the investigation into the pathogenesis of systemic lupus erythematous, in which the deficient suppressor T cell function plays a critical role.