DONOR-SPECIFIC CYTOTOXICITY INDUCED BY ALLOGENEIC INTESTINAL EPITHELIAL-CELLS IN A SPONGE MATRIX MODEL

Small intestinal epithelial cells (IEC) constitutively express MHC cla ss II molecules. However, little is known about the role of IEC in int estinal allograft rejection. The present study examined whether IEC ca n induce the development of cytotoxic T cells in vivo using a sponge m atrix model. IEC isolated from ACI (RT1(a)) rats were injected into po lyurethane sponges implanted i. p. in Lewis (RT1(1)) rats. Sponge graf ts with ACI splenocytes or Lewis IEC were used as controls. The sponge grafts were removed and sponge-infiltrating cells (SIC) were harveste d on post-operative days (POD) 7, 10, and 14. The phenotype of SIC was determined by FACS analysis and the cell-mediated cytotoxicity was me asured using a chromium release assay. Non-specific inflammatory cells accumulated in the IEC sponge allografts during the first 10 days. By POD 14, however, 61 % of SIC were T lymphocytes and 36 % expressed cy totoxic T cell marker (OX-8). The cytotoxicity in IEC sponge allograft s was detectable on POD 7 and POD 10, and markedly elevated on POD 14. The cytotoxicity induced by allogeneic splenocytes appeared in the sp onge grafts on POD 7, peaked on POD 10, and declined thereafter. The a llospecific cytotoxicity induced by IEC was dependent on host macropha ges as pretreatment of animals with gadolinium, a rare earth metal tha t inactivates macrophages, abrogated the induction of cytotoxicity. We conclude that: (1) the migration and maturation of cytotoxic T cells can be induced in vivo by IEC and (2) IEC may contribute to the increa sed severity of intestinal rejection through interaction with macropha ges.