The long term objective is to elucidate the mechanisms of immune responses in the intestine leading to rejection and killing of intestinal pathogens. Intestinal helminths cause significant diseases in man and domestic animals and are informative probes of intestinal immune function. In a well characterized model of intestinal infection with Trichinella spiralis, the OX8- OX22+ T helper cells have been shown to originate in the small intestine and to activate peripheral B lymphocytes. This application seeks funding for three years to support a project that will examine the activation effect of this subset of T helper cells on antibody-producing B cells in the gut during an early stage of infection. The investigation involves the filter immunoplaque assay and immunofluorescence assay. These studies differ substantially from previous work in that, 1) antigen-specific antibody-producing B cells generated in the traditionally neglected non-Peyer's patch regions of the small intestine will be analyzed; 2) intestinal B cells producing antibodies other than IgA isotype will be studied; 3) a rapid (within a week) antibody response stimulated by the T helper cells will be characterized. There are three specific aims to this proposal. 1 . Analysis of interactions between protective T helper cells of the OX8- OX22- subset and antibody-producing B cells in the intestine. 2. Classification of isotype specificity of intestinal antibody-producing cells elicited by T helper cells. 3. Examination of tissue distribution of antigen-specific antibody-producing cells in the intestine. These experiments will generate broadly applicable information about protective B cell responses during infection caused by complex intestinal pathogens. This information could be used to direct immunization strategy and immunological therapy against such infections.
