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. 1992 Oct;90(1):111–116. doi: 10.1111/j.1365-2249.1992.tb05841.x

Renal allograft rejection: induction and function of adhesion molecules on cultured epithelial cells.

Y Lin 1, J A Kirby 1, K Clark 1, B K Shenton 1, J L Forsythe 1, G Proud 1, R M Taylor 1
PMCID: PMC1554530  PMID: 1382902

Abstract

The interaction of graft-infiltrating immune cells with donor parenchymal cells is an important early event in allograft rejection. This binding is stabilized by interaction of antigen-independent 'adhesion' molecules expressed on the two cell types. As the level of expression of these molecules can be altered during inflammation, a series of experiments was performed to examine the effects of the inflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on adhesion molecules expressed by cultured human renal tubular epithelial cells. These cells constitutively expressed ICAM-1 and LFA-3. Incubation with IFN-gamma increased expression of ICAM-1 but had no significant effect on expression of LFA-3 (P greater than 0.05). Incubation with TNF-alpha increased expression of both ICAM-1 and LFA-3; IFN-gamma synergized with TNF-alpha to further augment expression of these molecules. Peripheral blood lymphocytes (PBL) showed an enhanced binding to allogeneic renal epithelial cell monolayers which had been pretreated with IFN-gamma or TNF-alpha. MoAbs specific for ICAM-1 or its ligand LFA-1 inhibited adhesion of PBL to either IFN-gamma- or TNF-alpha-pretreated renal cells. By contrast, antibodies specific for LFA-3 or its ligand CD2 only significantly blocked PBL adhesion to renal cells which had been pretreated with TNF-alpha. Combination of antibodies specific for multiple components of the adhesion systems produced greater inhibition of adhesion than was produced by any single MoAb. These results suggest that the inflammatory cytokines IFN-gamma and TNF-alpha up-regulate expression of functional ICAM-1 and LFA-3 molecules which can augment the binding of potentially graft-damaging lymphoid cells to renal tubular epithelial cells.

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Selected References

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  1. Aggarwal B. B., Eessalu T. E., Hass P. E. Characterization of receptors for human tumour necrosis factor and their regulation by gamma-interferon. Nature. 1985 Dec 19;318(6047):665–667. doi: 10.1038/318665a0. [DOI] [PubMed] [Google Scholar]
  2. Bishop G. A., Hall B. M. Expression of leucocyte and lymphocyte adhesion molecules in the human kidney. Kidney Int. 1989 Dec;36(6):1078–1085. doi: 10.1038/ki.1989.303. [DOI] [PubMed] [Google Scholar]
  3. Bonnefoy-Bérard N., Vincent C., Revillard J. P. Antibodies against functional leukocyte surface molecules in polyclonal antilymphocyte and antithymocyte globulins. Transplantation. 1991 Mar;51(3):669–673. doi: 10.1097/00007890-199103000-00024. [DOI] [PubMed] [Google Scholar]
  4. Böyum A. A one-stage procedure for isolation of granulocytes and lymphocytes from human blood. General sedimentation properties of white blood cells in a 1g gravity field. Scand J Clin Lab Invest Suppl. 1968;97:51–76. [PubMed] [Google Scholar]
  5. Cosimi A. B., Conti D., Delmonico F. L., Preffer F. I., Wee S. L., Rothlein R., Faanes R., Colvin R. B. In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts. J Immunol. 1990 Jun 15;144(12):4604–4612. [PubMed] [Google Scholar]
  6. David V., Leca G., Corvaia N., Le Deist F., Boumsell L., Bensussan A. Proliferation of resting lymphocytes is induced by triggering T cells through an epitope common to the three CD18/CD11 leukocyte adhesion molecules. Cell Immunol. 1991 Sep;136(2):519–524. doi: 10.1016/0008-8749(91)90372-i. [DOI] [PubMed] [Google Scholar]
  7. Faull R. J., Russ G. R. Tubular expression of intercellular adhesion molecule-1 during renal allograft rejection. Transplantation. 1989 Aug;48(2):226–230. doi: 10.1097/00007890-198908000-00009. [DOI] [PubMed] [Google Scholar]
  8. Franke W. W., Weber K., Osborn M., Schmid E., Freudenstein C. Antibody to prekeratin. Decoration of tonofilament like arrays in various cells of epithelial character. Exp Cell Res. 1978 Oct 15;116(2):429–445. doi: 10.1016/0014-4827(78)90466-4. [DOI] [PubMed] [Google Scholar]
  9. Hall B. M., Bishop G. A., Duggin G. G., Horvath J. S., Philips J., Tiller D. J. Increased expression of HLA-DR antigens on renal tubular cells in renal transplants: relevance to the rejection response. Lancet. 1984 Aug 4;2(8397):247–251. doi: 10.1016/s0140-6736(84)90297-6. [DOI] [PubMed] [Google Scholar]
  10. Hall B. M. Cells mediating allograft rejection. Transplantation. 1991 Jun;51(6):1141–1151. doi: 10.1097/00007890-199106000-00001. [DOI] [PubMed] [Google Scholar]
  11. Heagy W., Waltenbaugh C., Martz E. Potent ability of anti-LFA-1 monoclonal antibody to prolong allograft survival. Transplantation. 1984 May;37(5):520–523. doi: 10.1097/00007890-198405000-00021. [DOI] [PubMed] [Google Scholar]
  12. Hildreth J. E., August J. T. The human lymphocyte function-associated (HLFA) antigen and a related macrophage differentiation antigen (HMac-1): functional effects of subunit-specific monoclonal antibodies. J Immunol. 1985 May;134(5):3272–3280. [PubMed] [Google Scholar]
  13. Hoffman S., Edelman G. M. Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5762–5766. doi: 10.1073/pnas.80.18.5762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Häyry P., von Willebrand E. The influence of the pattern of inflammation and administration of steroids on class II MHC antigen expression in renal transplants. Transplantation. 1986 Oct;42(4):358–363. doi: 10.1097/00007890-198610000-00005. [DOI] [PubMed] [Google Scholar]
  15. Hünig T., Tiefenthaler G., Meyer zum Büschenfelde K. H., Meuer S. C. Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand. Nature. 1987 Mar 19;326(6110):298–301. doi: 10.1038/326298a0. [DOI] [PubMed] [Google Scholar]
  16. Ikuta S., Kirby J. A., Shenton B. K., Givan A. L., Lennard T. W. Human endothelial cells: effect of TNF-alpha on peripheral blood mononuclear cell adhesion. Immunology. 1991 May;73(1):71–76. [PMC free article] [PubMed] [Google Scholar]
  17. Ishikura H., Takahashi C., Kanagawa K., Hirata H., Imai K., Yoshiki T. Cytokine regulation of ICAM-1 expression on human renal tubular epithelial cells in vitro. Transplantation. 1991 Jun;51(6):1272–1275. doi: 10.1097/00007890-199106000-00024. [DOI] [PubMed] [Google Scholar]
  18. Kirby J. A., Forsythe J. L., Simm A., Proud G., Taylor R. M. Renal allograft rejection: protection of renal tubular epithelial cells from lymphokine activated killer cell mediated lysis by pretreatment with cytokines. Nephrol Dial Transplant. 1989;4(9):824–828. [PubMed] [Google Scholar]
  19. Kirby J. A., Ikuta S., Clark K., Proud G., Lennard T. W., Taylor R. M. Renal allograft rejection: investigation of alloantigen presentation by cultured human renal epithelial cells. Immunology. 1991 Mar;72(3):411–417. [PMC free article] [PubMed] [Google Scholar]
  20. Lapierre L. A., Fiers W., Pober J. S. Three distinct classes of regulatory cytokines control endothelial cell MHC antigen expression. Interactions with immune gamma interferon differentiate the effects of tumor necrosis factor and lymphotoxin from those of leukocyte alpha and fibroblast beta interferons. J Exp Med. 1988 Mar 1;167(3):794–804. doi: 10.1084/jem.167.3.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Martin S., Brenchley P. E., O'Donoghue D. J., Dyer P. A., Mallick N. P., Johnson R. W. The identification of allo- and auto-lymphocytotoxic antibodies in serum, in the presence of rabbit antithymocyte globulin. Tissue Antigens. 1988 Jan;31(1):26–32. doi: 10.1111/j.1399-0039.1988.tb02061.x. [DOI] [PubMed] [Google Scholar]
  22. Sanders M. E., Makgoba M. W., Sharrow S. O., Stephany D., Springer T. A., Young H. A., Shaw S. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol. 1988 Mar 1;140(5):1401–1407. [PubMed] [Google Scholar]
  23. Springer T. A., Dustin M. L., Kishimoto T. K., Marlin S. D. The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol. 1987;5:223–252. doi: 10.1146/annurev.iy.05.040187.001255. [DOI] [PubMed] [Google Scholar]
  24. Stolpen A. H., Guinan E. C., Fiers W., Pober J. S. Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human vascular endothelial cell monolayers. Am J Pathol. 1986 Apr;123(1):16–24. [PMC free article] [PubMed] [Google Scholar]
  25. Suranyi M. G., Bishop G. A., Clayberger C., Krensky A. M., Leenaerts P., Aversa G., Hall B. M. Lymphocyte adhesion molecules in T cell-mediated lysis of human kidney cells. Kidney Int. 1991 Feb;39(2):312–319. doi: 10.1038/ki.1991.39. [DOI] [PubMed] [Google Scholar]

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