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Transplantation Immunology pp 145–156Cite as

Direct and Indirect Allorecognition

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Part of the book series: Methods In Molecular Biology™ ((MIMB,volume 333))

Abstract

The design and effectiveness of strategies to promote long-term graft acceptance requires a fundamental understanding of the mechanisms underlying acute and chronic rejection. This chapter discusses the two pathways of allorecognition-direct and indirect-and suggests that the direct pathway plays a major role in the early weeks after transplantation and that the indirect pathway may contribute to the process of chronic rejection. The results of in vitro and in vivo experimental models are discussed, together with clinical data.

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References

  1. Bach F., Bach M., and Sondel P. (1976) Differential function of major histocompatibility complex antigens in T lymphocyte activation. Nature 259, 273–281.

    Article  CAS  PubMed  Google Scholar 

  2. Skinner M. and Marbrook J. (1976) An estimation of the frequency of frequency of precursor cells which generate cytotoxic lymphocytes. J. Exp. Med. 143, 1562–1567.

    Article  CAS  PubMed  Google Scholar 

  3. Fischer-Lindahl K. and Wilson D. (1976) J. Exp. Med. 145, 500–507.

    Article  Google Scholar 

  4. Hunig T. and Bevan M. (1980) Self-H2 antigens influence the specificity of alloreactive cells. J. Exp. Med. 151, 1288–1298.

    Article  CAS  PubMed  Google Scholar 

  5. Lombardi G., Sidhu S., Batchelor J., and Lechler R. (1989) Allorecognition of DR1 by T cells from a DR/Dw13 responder mimics self-restricted recognition of endogenous peptides. Proc. Natl. Acad. Sci. 86, 4190–4194.

    Article  CAS  PubMed  Google Scholar 

  6. Lombardi G., Sidhu S., Daly M., Batchelor J., Makgoba W., and Lechler R. (1990) Are primary alloresponses truly primary? Int. Immunol. 2, 9–13.

    Article  CAS  PubMed  Google Scholar 

  7. Matzinger P. and Bevan M. (1977) Why do so many lymphocytes respond to major histocompatibility antigens? Cell. Immunol. 29, 1–5.

    Article  CAS  PubMed  Google Scholar 

  8. Bevan M. (1984) High determinant density may explain the phenomenon of alloreactivity. Immunol. Today 5, 128–130.

    Article  Google Scholar 

  9. Harding C. and Unanue E. (1990) Quantitation of antigen-presenting cell MHC class II/peptide complexes necessary for T cell stimulation. Nature 346, 574.

    Article  CAS  PubMed  Google Scholar 

  10. Lechler R., Lombardi G., Batchelor J., Reinsmoen N., and Bach F. (1990) The molecular basis of alloreactivity. Immunol. Today 11, 83–88.

    Article  CAS  PubMed  Google Scholar 

  11. Merkenschlager M., Graf D., Lovatt M., Bommhardt U., Zamoyska R., and Fisher A. (1997) How many thymocytes audition for selection? J. Exp. Med. 186,1149–1158.

    Article  CAS  PubMed  Google Scholar 

  12. Pietra B., Wiseman A., Bolwerk A., Rizeq M., and Gill R. (2000) CD4 T cellmediated cardiac allograft rejection requires donor but not host MHC class II. J. Clin. Invest. 106, 1003–1010.

    Article  CAS  PubMed  Google Scholar 

  13. Braun M., McCormack A., Webb G., and Batchelor J. (1993) Mediation of acute but not chronic rejection of the MHC incompatible rat kidney grafts by alloreactive CD4 T cells activated by the direct pathway of sensitisation. Transplantation 55, 177–182.

    Article  CAS  PubMed  Google Scholar 

  14. Austyn J. and Larsen C. (1990) Migration patterns of dendritic leucocytes. Implications for transplantation. Transplantation 49, 1–7.

    Article  CAS  PubMed  Google Scholar 

  15. Harding F. and Allison J. (1993) CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help. J. Exp. Med. 176, 519–529.

    Google Scholar 

  16. Dai R., Grammar S., and Streilein J. (1993) Fresh and cultured Langerhans cells display differential capacities to activate hapten-specific T cells. J. Immunol. 150, 59–66.

    CAS  PubMed  Google Scholar 

  17. Streilein J., Grammar S., Yoshikawa T., Demidem A., and Vermeer M. (1990) Functional dichotomy between Langerhans cells that present antigen to naive and to memory/effector T lymphocytes. Immunol. Rev. 117, 159–183.

    Article  CAS  PubMed  Google Scholar 

  18. Milton A., Spencer S., and Fabre J. (1986) The effects of cyclosporin A on the induction of donor class I and class II MHC antigens in heart and kidney allografts in the rat. Transplantation 42, 337.

    Article  CAS  PubMed  Google Scholar 

  19. Hosenpud J., Shipley J., and Wagner C. (1992) Cardiac allograft vasculopathy, Current concepts, recent developments and future directions. J. Heart Lung Transplant. 11, 9–23.

    CAS  PubMed  Google Scholar 

  20. Deacock S. J. and Lechler R. L. (1992) Positive correlation of T cell sensitization with frequencies of alloreactive T helper cells in chronic renal failure patients. Transplantation 54, 338–343.

    Article  CAS  PubMed  Google Scholar 

  21. Mason P., Robinson C., and Lechler R. (1996) Detection of donor-specific hyporesponsiveness following late failure of human renal allografts. Kidney Int. 50, 1019–1025.

    Article  CAS  PubMed  Google Scholar 

  22. Cramer D., Chapman F., Wu G., Harnaha J., Quian S., and Makowka L. (1990) Cardiac transplantation in the rat. II. Alteration of the severity of donor graft arteriosclerosis by modulation of the host immune response. Transplantation 50, 554–558.

    Article  CAS  PubMed  Google Scholar 

  23. Shin Y., Adams D., Wyner L., Akalin E., Sayegh M., and Karnovsky M. (1995) Intrathymic tolerance in the Lewis-to-F344 chronic cardiac allograft rejection model. Transplantation 59, 1647–1653.

    Article  CAS  PubMed  Google Scholar 

  24. Cramer D., Qian S., Harnaha J., et al. (1989) Cardiac transplantation in the rat, I. The effect of histocompatibility differences on graft atherosclerosis. Transplantation 47, 414–419.

    Article  CAS  PubMed  Google Scholar 

  25. Isoniemi H., Nurminen M., Tikkanen M., et al. (1994) Risk factors predicting chronic rejection of renal allografts. Transplantation 57, 68–72.

    Article  CAS  PubMed  Google Scholar 

  26. Lechler R. and Batchelor J. (1982) Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J. Exp. Med. 155, 31–41.

    Article  CAS  PubMed  Google Scholar 

  27. Benichou G., Takizawa A., Olson A., McMillan M., and Sercarz E. (1992) Donor major histocompatibility complex (MHC) peptides are presented by recipient MHC molecules during graft rejection. J. Exp. Med. 175, 305–308.

    Article  CAS  PubMed  Google Scholar 

  28. Fangmann J., Dalchau R., and Fabre J. (1992) Rejection of skin allografts by indirect allorecognition of donor class I major histocompatibility complex peptides. J. Exp. Med. 175, 1521–1529.

    Article  CAS  PubMed  Google Scholar 

  29. Benham A., Sawyer G., and Fabre J. (1995) Indirect T cell recognition of donor antigens contributes to the rejection of vascularized kidney allografts. Transplantation 59, 1028–1032.

    Article  CAS  PubMed  Google Scholar 

  30. Grusby M., Johnson R., Papaioannou V., and Glimcher L. (1991) Depletion of CD4 T cells in major histocompatibility complex class II-deficient mice. Science 253, 1417–1420.

    Article  CAS  PubMed  Google Scholar 

  31. Auchinloss H. J., Lee R., Shea S., Markowitz J., Grusby M., and Glimcher L. (1993) The role of ‘indirect’ recognition in initiating rejection of skin grafts from major histocompatibility complex class II-deficient mice. Proc. Natl. Acad. Sci. USA 90, 3373–3377.

    Article  Google Scholar 

  32. Sayegh M., Perico N., Gallon L., Imberti O., Hancock W., Remuzzi G., et al. (1994) Mechanisms of acquired thymic unresponsiveness to renal allografts. Transplantation 58, 125–132.

    CAS  PubMed  Google Scholar 

  33. Chicz R., Urban R., Lane W., Gorga S., Stern L., Vignali D., et al. (1992) Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC relayed molecules and are heterogeneous in size. Nature 358, 764–768.

    Article  CAS  PubMed  Google Scholar 

  34. Essaket S. and Fabron J. (1990) Co-recognition of HLA-A1 and HLA DPw3 by a human CD4+ alloreactive T cell clone. J. Exp. Med. 172, 387–390.

    Article  CAS  PubMed  Google Scholar 

  35. de Koster H., Anderson D., Termijtelen A. (1990) T cells sensitized to synthetic HLA-DR3 peptide give evidence of continuous presentation of denatured HLADR3 molecoles by HLA-DP. J. Exp. Med. 169, 1191–1196.

    Article  Google Scholar 

  36. Hart D. and Fabre J. (1979) Quantitative studies on the tissue distribution of Ia and SD antigens in the DA and Lewis rat strains. Transplantation 27, 110.

    Article  CAS  PubMed  Google Scholar 

  37. Milton A., Spencer S., and Fabre J. (1986) Massive induction of donor type class I and class II MHC antigens in rejecting cardiac allografts in the rat. J. Exp. Med. 161, 98.

    Article  Google Scholar 

  38. Auchinloss H. J. and Sutan H. (1996) Antigen processing and presentation in transplantation. Curr. Opin. Immunol. 8, 681–687.

    Article  Google Scholar 

  39. Joos J., Zanker B., Wagnar H., and Kabelitz D. (1988) Quantitative assessment of interleukin-2-producing alloreactive human T cells by limiting dilution analysis. J. Immunol. Methods 112, 85.

    Article  Google Scholar 

  40. Liu Z., Sun Y., Xi Y., Maffai A., Reed E., Harri,s P., et al. (1993) Contribution of direct and indirect allorecognition pathways to T cell alloreactivity. J. Exp. Med. 177, 1643–1650.

    Article  CAS  PubMed  Google Scholar 

  41. Van Besouw N., Vaessen L., Daane C., Jutte N., Balk A., Claas F., et al. (1996) Peripheral monitoring of direct and indirect alloantigen presentation pathways in clinical heart transplant recipients. Transplantation 61, 165–167.

    Article  PubMed  Google Scholar 

  42. Liu Z., Coloval A., Tugulea S., Reed E., Fisher P., Mancini D., et al. (1996) Indirect recognition of donor HLA-DR peptides in organ allograft rejection. J. Clin. Invest. 98, 1150–1157.

    Article  CAS  PubMed  Google Scholar 

  43. Frasca L., Amendola A., Hornick P., Uren J., Marelliberg F., Lechler R., et al. (1998) The role of donor and recipient antigen presenting cells in priming and maintaining T cells with indirect specificity. Transplantation 66, 1238–1243.

    Article  CAS  PubMed  Google Scholar 

  44. Taylor D., Ibrahim H., Tolman D., and Hess M. (1991) Accelerated coronary arteriosclerosis in cardiac transplantation. Transplant. Rev. 5, 165–174.

    Article  Google Scholar 

  45. Russell P., Chase C., Winn H., and Colvin R. (1994) Coronary atherosclerosis in transplanted rat heart. II. The importance of humoral immunity. J. Immunol. 152, 389–398.

    Google Scholar 

  46. Dunn M. J., Crisp S. J., Rose M. L., Taylor P. M., Yacoub M. H. (1992) Antiendothelial antibodies and coronary artery disease after cardiac transplantation. Lancet. 339, 1566–1570.

    Article  CAS  PubMed  Google Scholar 

  47. Reed E. F., Hong B., Ho E., Harris P. E., Weinberger J., Suciu-Foca N. (1996) Monitoring of soluble HLA alloantigens and anti-HLA antibodies identifies heart allograft recipients at risk of transplant-associated coronary artery disease. Transplantation. 61, 566–572.

    Article  CAS  PubMed  Google Scholar 

  48. Bradley J., Mowat A. M., and Bolton E. (1992) Processed MHC class I alloantigen as the stimulus for CD4+ T-cell dependent antibody-mediated graft rejection. Immunol. Today 13(11), 434–438.

    Article  CAS  PubMed  Google Scholar 

  49. Simitsek P., Campbell D., Lanzavecchia A., Fairweather N., and Watts C. (1995) Modulation of antigen processing by bound antibodies can boost or suppress class II major histocompatibility complex presentation of different T cell determinants. J. Exp. Med. 181, 1957.

    Article  CAS  PubMed  Google Scholar 

  50. Sallusto F. and Lanzavecchia A. (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and down regulated by tumour necrosis factor alpha. J. Exp. Med. 179, 1109.

    Article  CAS  PubMed  Google Scholar 

  51. Benzaquen L., Nicholson-Weller A., and Halperin J. (1994) Terminal complement proteins C5b-9 release fibroblast growth factor and platelet derived growth factor from endothelial cells. J. Exp. Med. 179, 985–992.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College Hammersmith Campus, London, England

    Philip Hornick

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  1. Philip Hornick
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Editor information

Editors and Affiliations

  1. National Heart and Lung Institute, London, UK

    Philip Hornick

  2. National Heart and Lung Institute, Harefield, UK

    Marlene Rose

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© 2006 Humana Press Inc.

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Hornick, P. (2006). Direct and Indirect Allorecognition. In: Hornick, P., Rose, M. (eds) Transplantation Immunology. Methods In Molecular Biology™, vol 333. Humana Press. https://doi.org/10.1385/1-59745-049-9:145

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  • DOI: https://doi.org/10.1385/1-59745-049-9:145

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-544-6

  • Online ISBN: 978-1-59745-049-2

  • eBook Packages: Springer Protocols

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