Analysis of murine Ialpha-restricted CD4+ T cell clones has demonstrated that such clones can be divided into two subsets (Th1 and Th2 clones) based upon types of lymphokines secreted and upon functional activity. The division of CD4+ T cells into such subsets may be of fundamental importance in the regulation of isotype specific responses and in the regulation of responses to different types of pathogens. Selective loss or absence of one subset may result in susceptibility to specific types of infection, while selective increase in one subset may result in autoimmune disease or allergy. The existence of CD4+ T cell subsets, though well established in mice, has not been well studied in man. The purpose of this proposal is to: 1. define the subtypes of human CD4+ T cell clones, and to determine under what conditions each subtype is preferentially stimulated. 2. examine how these subtypes of T cell clones regulate isotype specific responses in Beta cells. 3. determine how CD4+ T cell clones may be involved in the pathogenesis of allergic disease. To study these problems, our lab has developed the capacity to generate and maintain antigen specific human T cell clones, propagated in the absence of mitogens. We already have available a panel of CD4+ T cell clones, which are heterogeneous in patterns of lymphokine synthesis and in function. These patterns are distinctly different from those seen in mice. Second, we have developed a system using human T cell clones for the induction of Ig synthesis in Beta cells under cognate conditions, which give results far superior to that seen with mitogens. To evaluate Ig production, we have developed sensitive assays for human IgE, IgA, IgM, IgG and IgG subclasses. Finally, we have enlisted the support of other investigators to help us apply molecular biology techniques to the analysis of our clones, and to provide us with reagents necessary to evaluate the cellular interactions involved in the induction of Ig synthesis.
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