Abstract
Small intestinal epithelial cells (IEC) constitutively express MHC class II molecules. However, little is known about the role of IEC in intestinal allograft rejection. The present study examined whether IEC can induce the development of cytotoxic T cells in vivo using a sponge matrix model. IEC isolated from ACI (RT1a) rats were injected into polyurethane sponges implanted i.p. in Lewis (RT11) rats. Sponge grafts with ACI splenocytes or Lewis IEC were used as controls. The sponge grafts were removed and sponge-infiltrating cells (SIC) were harvested on post-operative days (POD) 7, 10, and 14. The phenotype of SIC was determined by FACS analysis and the cell-mediated cytotoxicity was measured 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 cytotoxic T cell marker (OX-8). The cytotoxicity in IEC sponge allografts was detectable on POD 7 and POD 10, and markedly elevated on POD 14. The cytotoxicity induced by allogeneic splenocytes appeared in the sponge grafts on POD 7, peaked on POD 10, and declined thereafter. The allospecific cytotoxicity induced by IEC was dependent on host macrophages as pretreatment of animals with gadolinium, a rare earth metal that 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 increased severity of intestinal rejection through interaction with macrophages.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ascher NL, Chen S, Hoffman RA, Stimmons RL (1983) Maturation of cytotoxic T cells within sponge matrix allografts. J Immunol 131:617–621
Bishop DK, Jutila MA, Sedmak DD, Beattie MS, Orosz CG (1989) Lymphocyte entry into inflammatory tissues in vivo: qualitative differences of high endothelial venule-like vessels in sponge matrix allografts vs isografts. J Immunol 142:4219–4225
Bishop GA, Waugh JA, Hall BM (1988) Expression of HLA antigens on renal tubular cells in culture. Transplantation 46:303–310
Bjerknes M, Cheng H (1981) Methods for the isolation of intact epithelium from the mouse intestine. Anat Rec 199: 565–574
Bland P (1988) MHC class II expression by the gut epithelium. Immunol Today 9:174–178
Bumgardner GL, Chen S, Hoffman R, Cahill DC, So SK, Platt J, Bach FH, Ascher NL (1989) Afferentand efferent pathways in T cells responses to MHC class I+,II-hepatocytes. Transplantation 47:163–170
Bumgardner GL, Chen S, Almond SP, Ascher NL, Payne WD, Matas AJ (1990) Role of macrophages in the immune response to hepatocytes. J Surg Res 48:568–572
Bumgardner GL, Matas AJ, Chen S, Cahill D, Cunningham TR, Payne WD, Bach FH, Ascher NL (1990) Comparison of in vivo and in vitro immune response to purified hepatocytes. Transplantation 49:429–435
Callery MP, Kamei T, Flye MW (1989) Kupffer cell blockage inhibits induction of tolerance by the portal venous route. Transplantation 47:1092–1093
Canadian Council on Animal Care (1984) Guide to the care and use of experimental animals, vol 1. Association of Universities and Colleges of Canada, Ottawa, Canada
Golding H, Singer A (1984) Role of accessory cell processing and presentation of shed H-2 alloantigens in allospecific cytotoxic T lymphocyte responses. J Immunol 133:597–605
Gundlach M, Wasfie T, DÁgati V, Chabot J, Oluwole S, Hardy MA (1991) The role of passenger leukocytes in the immunogenicity of intestinal and cardiac allografts in the rat. Transplant Proc 23: 187–188
Hadley GA, Linders B, Mohanakumar T (1992) Immunogenicity of MHC class I alloantigens expressed on parenchymal cells in the human kidney. Transplantation 54:537–542
Hanto DW, Hopt UT, Hoffman R, Simmons RL (1982) Recruitment of unsensitized circulating lymphocytes to sites of allogeneic cellular interactions. Transplantation 33:541–546
Ingham Clark CL, Cunningham AJ, Crane PW, Wood RFM, Lear PA (1990) Lymphocyte infiltration patterns in rat small-bowel transplants. Transplant Proc 22:2460
Kim PO, Levy GA, Craig M, Cullen J, Cohen Z (1990) Immune responses during small intestinal allograft rejection: correlation between procoagulant activity and histopathology. Transplant Proc 22:2477–2479
Li XC, Quan D, Duff J, Grant D (1992) Rat intestinal epithelial cells as accessory cells in alloimmune responses. Transplant Proc 24:1149
Mayer L (1987) The role of epithelial cells as accessory cells. Adv Exp Med Biol 216A:209–218
Mueller DL, Jenkins MK, Schwartz RH (1989) Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol 7:445–480
Orosz CG, Bishop DK, Ferguson RM (1989) In vivo mechanisms of alloreactivity. VI. Evidence that alloantigen deposition initiates both local and systemic mechanisms that influence CTL accumulation at a graft site. Transplantation 48:818–824
Robarts PJ, Häyry P (1976) Sponge matrix allografts: a model for analysis of killer cells infiltrating mouse allografts. Transplantation 21:437–445
Roland CR, Mangino MJ, Duffy BF, Flye MW (1993) Lymphocyte suppression by Kupffer cells prevents portal venous tolerance induction: a study of macrophage function after intravenous gadolinium. Transplantation 55:1151–1158
Rosemurgy AS, Schraut WH (1986) Small bowel allografts: sequence of histologic changes in acute and chronic rejection. Am J Surg 151:470–475
Schmid T, Oberhuber G, Korozsi G, Klima G, Margreiter R (1990) Altered distribution of MHC class II antigens on enterocytes during acute small bowel allograft rejection in rats. Transpl Int 3: 73–77
Schmid T, Oberhuber G, Koroszi G, Klima G, Margreiter R (1990) MHC class II antigens are expressed by enterocytes lining the crypts of Lieberkuhn during initial phases of rejection. Transplant Proc 22:2064–2065
Stangl MJ, Lee KKW, Lee TK, Moynihan HL, Schraut WH (1990) Graft pretreatment with monoclonal antibodies prior to small-bowel transplantation. Transplant Proc 22:2483–2484
Steinman RM, Young JW (1991) Signals arising from antigen-presenting cells. Curr Opinion Immunol 3:361–372
Todo S, Tzakis AG, Abu-Elmagd K, Reyes J, Nakamura K, Casavilla A, Selby R, Nour BM, Wright H, Fung JJ, Demetris AJ, Van Thiel DH, Starzl TE (1992) Intestinal transplantation in composite visceral grafts or alone. Ann Surg 216:223–234
Tsokos GC, Stocks NI, Clerici M, Shearer GM (1990) Human in vitro allogeneic responses. J Immunol 144: 2524–2528
Weaver CT, Unanue ER (1990) The costimulatory function of antigen-presenting cells. Immunol Today 11:49–59
Weinberger O, Germain RN, Springer T, Burakoff SJ (1993) Role of syngeneic Ia+accessory cells in the generation of allospecific CTL responses. J Immunol 129:694–697
Author information
Authors and Affiliations
About this article
Cite this article
Li, XC., Zhong, R., Zhu, L. et al. Donor-specific cytotoxicity induced by allogeneic intestinal epithelial cells in a sponge matrix model. Transpl Int 8, 13–19 (1995). https://doi.org/10.1007/BF00366705
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00366705