REGULATION OF REAGINIC ANTIBODY RESPONSE

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The purpose of this research is to elucidate the mechanisms involved in the regulation of the IgE response, and to find some maneuvors to suppress the IgE antibody formation to allergens. During the current grant period, we found that a lipocortin-like lymphokine, i.e., glycosylation inhibiting factor (GIF), suppressed the primary IgE and IgG antibody responses in the mouse, and diminished the on-going IgE antibody formation. Analysis of cellular mechanisms for the immunosuppression indicated that GIF facilitated the generation of antigen-specific suppressor T cells which formed their own GIF. In the present proposal, attempts will be made to generate antigen-specific suppressor T cells in vitro from antigen-primed T cells, and to elucidate the cellular and molecular mechanisms involved. Experiments will be carried out to determine whether GIF may change the function of antigen-primed T cells, and may affect the antigen-presenting cells. It was also shown that antigen-specific suppressor T cells form GIF which has affinity for the antigen, and that the antigen- specific GIF suppresses the in vivo antibody response in a carrier- specific manner. Mouse T cell hybridomas were constructed from an ovalbumin-primed mouse T cell clone. One of the T cell hybridomas form antigen-specific GIF upon incubation with antigen-pulsed syngenic macrophages. In this proposal, antigen- specific GIF will be obtained from the T cell hybridomas, and physicochemical properties of the molecules will be characterized. Comparisons will be made between the antigen- specific GIF and antigen-specific T suppressor factor (TsF) described by other investigators. Analysis will be made to determine whether the MHC compatibility between the cell source of antigen-specific GIF and target cells is essential for the carrier-specific suppression. Based on the findings obtained in mouse lymphocyte systems, attempts will be made to generate antigen-specific suppressor T cells in vitro from the peripheral blood T cells of allergic patients, and to construct human antigen- specific T cell hybridomas which will produce allergen-specific GIF that may suppress the antibody response to the allergen.