Because of the inaccessability of the intestinal tract, experiments concerning the immunological responses at that site have been difficult to design. Some of these difficulties could be circumvented by transplanting fetal small intestine to the dorsum of syngeneic adult rats. Using small intestinal transplant model, we propose to examine: (1) the time course of specific antibody production and (2) suppression of systemic immune responses following intestinal immunization. We will test the hypothesis that the immunization of the transplanted intestine will lead to the following: migration of B and T lymphocytes to the regional lymph nodes (aortic and paravertebral); these lymphocytes will then migrate sequentially to the thoracic duct (TD), systemic circulation and lamina propria of the transplanted intestines. Part of the IgA produced by these cells in the lamina propria will be transported across the epithelium into the lumen and part will be absorbed and secreted into the bile of the recipient animal. The following experiments will be performed in this investigation: (1) Longitudinal evaluation by enzyme-linked immunosorbent assay of specific IgA and IgG antibodies in the lumen of the transplanted intestines and in the bile of the recipient animal following immunization of the transplants with cholera toxin and toxin related antigens. (2) Identification of the cells containing antibodies to cholera toxin using immunofluorescence microscopy in the TD lymph, mesenteric lymph nodes and aortic and paravertebral lymph nodes following immunization of the transplanted intestine with cholera toxin and toxin related antigens. In addition, we will test the hypothesis that lymphocytes migrating from the Peyer's patches of the transplanted intestine to the systemic circulation suppress systemic antibody response. The systemic antibody response will be evaluated by hemolytic plaque assay in the spleen. We will evaluate specific splenic plaque forming cells (PFC) in rats immunized initially via transplanted intestine and subsequently intraperitoneally with sheep red blood cells (SRBC). In order to clarify the mechanism by which intestinal immunization suppress systemic antibody response we will evaluate the specific splenic PFC responses in syngeneic animals receiving TD or splenic lymphocytes from animals immunized via transplanted intestines with SRBC. These studies will enhance our understanding of the functions of gastrointestinal lymphoid tissue.
