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Allograft rejection results from a failed attempt by the immune system to protect foreign tissue

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Abstract

The focus of our research is to understand the immune response to foreign tissue. We believe that adichotomy exists within the immune response to an allograft such that part of the response is dedicated to the protection of the graft. Nevertheless, in a dominantly graft-aggressive environment, rejection typically ensues. In this article, we describe models that have been set up to test directly the ability of potentially protective aspects of the immune response to prevent allograft rejection. We discussour data in the context of a growing body of exciting and often controversial literature.

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References

  1. Singer A, Bach FH: Allograft immunity: in vitro and in vivo studies; in Bach FH, Auchincloss H (eds) Transplantation Immunology, 1995, pp 105–111.

  2. Platt JL: Antibodies in graftrejection; in Bach FH, Auchincloss H (eds): Transplantation Immunology, 1995, pp 113–129.

  3. Sher A, Coffman R: Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu Rev Immunol 1992;10:385–409.

    Article  PubMed  CAS  Google Scholar 

  4. Romagnani S: Human Th1 and Th2 subsets: doubt no more. Immunol Today 1991;12:256, 257.

    Article  PubMed  CAS  Google Scholar 

  5. Hseih C-S, Heimberger AB, Gold JS, O'Garra A, Murphy K: Differential regulation of T helper phenotype development by IL-4 and IL-10 in an αβ-transgenic system. Proc Natl Acad Sci USA 1992;89: 6065–6069.

    Article  Google Scholar 

  6. Le Gros G, Ben-Sasson S, Seder R, Finkelman FD, Paul WE: Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med 1990;172: 921–929.

    Article  PubMed  Google Scholar 

  7. Swain SL, Weinberg AD, English M, Huston G: IL-4 directs the development of Th2-like helper effectors. J Immunol 1990;145: 3796–3806.

    PubMed  CAS  Google Scholar 

  8. Seder RA, Gazzinelli R, Sher A, Paul WE: Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc Natl Acad Sci USA 1993;90: 10,188–10,192.

    Article  CAS  Google Scholar 

  9. Manetti R, Parronchi P, Guidizi MG, Piccinni M-P, Maggi E, Trinchieri G, Romagnani S: Natural killer cell stimulatory factor interleukin 12 (IL-12) induces T helpertype (Th1)-specific immune responses and inhibits the development of IL-4-producing cells. J Exp Med 1993;177:1199–1204.

    Article  PubMed  CAS  Google Scholar 

  10. Inobe J, Slavin AJ, Komagata Y, Chen Y, Liu L, Weiner HL: IL-4 is a differentiation factor for transforminggrowth factor-betasecreting Th3 cells and oral administration of IL-4 enhances oral tolerance in experimental allergic encephalomyelitis. Eur J Immunol 1998;28:2780–2790.

    Article  PubMed  CAS  Google Scholar 

  11. Seddon B, Mason D: Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor-β and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4+ CD45RC− cells and CD4+ CD8− thymocytes. J Exp Med 1999;189:279–288.

    Article  PubMed  CAS  Google Scholar 

  12. Mueller R, Krahl T, Sarvetnick N: Pancreatic expression of interleukin-4 abrogates insulitis and autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med 1996;184:1093–1099.

    Article  PubMed  CAS  Google Scholar 

  13. Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL: Inhibition of Th1 responses prevents inflammatory bowel disease in seidmice reconstituted with CD45RB hi CD4+ T cells. Immunity 1994;1:553–562.

    Article  PubMed  CAS  Google Scholar 

  14. Powrie F, Carlino J, Leach MW, Mauze S, Coffman RL: Acritical role for transforming growth factor-β but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45 RB low CD4+ T cells. J Exp Med 1996; 183:2669–2674.

    Article  PubMed  CAS  Google Scholar 

  15. King C, Davies JD, Mueller R, Lee M-S, Krahl T, Yeung B, O'Connor E, Sarvetnick N. TGF-β1 alters APC preference, polarizing islet antigen responses to Th2. Immunity 1998;8:601–613.

    Article  PubMed  CAS  Google Scholar 

  16. O'Connell PJ, Pacheco-Silva A, Nickerson PW, Muggia RA, Bastos M, Kelley VR, Strom TB: Unmodified pancreatic isletallograftrejection results in the preferential expression of certain T cell activation transcripts. J Immunol 1993;150:1093–1104.

    PubMed  Google Scholar 

  17. Dallman MJ, Larsen CP, Morris PJ: Cytokinegene transcription in vascularised organ grafts: analysis usingsemiquantitative polymerase chain reaction. J Exp Med 1991; 174:493–496.

    Article  PubMed  CAS  Google Scholar 

  18. Bugeon L, Cuturi MC, Hallet MM, Paineau J, Chabannes D, Soulillou JP: Peripheral tolerance of an allograft in adult rats—characterization by low interleukin-2 and interferon-gamma mRNA levels and by strong accumulation of major histocompatibility complex transcripts in the graft. Transplantation 1992;54:219–225.

    Article  PubMed  CAS  Google Scholar 

  19. Takeuchi T, Lowry RP, Konieczny B: Heart allografts inmurine systems: the differential activation of Th2-like effector cells in peripheral tolerance. Transplantation 1992;53:1281–1294.

    Article  PubMed  CAS  Google Scholar 

  20. Sayegh MH, Akalin E, Hancock, WW, Russell ME, Carter CB, Linsley PS, Turka LA: CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2. J Exp Med 1995;181: 1869–1874.

    Article  PubMed  CAS  Google Scholar 

  21. Kupiec-Weglinski JW, Wasowska B, Papp I, Schmidbauer G, Sayegh MH, Baldwin WM III, Wieder KJ, Hancock WW: CD4 mAb therapy modulatesal loantibody production and intracardiac graft deposition in association with selective inhibition of Th1 lymphokines. J Immunol 1993;151:5053–5061.

    PubMed  CAS  Google Scholar 

  22. Mottram PL, Han WR, Purcell, LJ, McKenzie IF, Hancock WW: Increased expression of IL-4 and IL-10 and decreased expression of IL-2 and interferon-gamma in long-surviving mouse heart allograftsafter brief CD4-monoclonal antibody therapy. Transplantation 1995;59:559–565.

    PubMed  CAS  Google Scholar 

  23. Konieczny BT, Saleem S, Lowry RP, Lakkis FG: Vigorous allograft rejection in IFN gamma gene knockout mice (abstract) in Proceedings of the 15th Annual Meeting of the American Society of Transplant Physicians. Throfare, NJ, Slack Publishers, 1996, p 170.

    Google Scholar 

  24. Piccoti JR, Chan SY, Goodman RE, Magram J, Eichwald EJ, Bishop DK: IL-12 antagonism induces Th2 responses, yet exacerbatescardiac allograft rejection: evidence against a dominant protective role for Th2 cytokines inalloimmunity. J Immunol 1996;157:1951–1957.

    Google Scholar 

  25. Lowry RP, Konieczny B, Alexander D, Larsen C, Pearson T, Smith S, Narula S: Interleukin-10 enhances anti-CD3 monoclonal antibody-induced mortality and prolongs heartallograft survival in inbred mice. Gransplant Proc 1995;27:392–394.

    CAS  Google Scholar 

  26. Zheng XX, Steele AW, Nickerson PW, Steurer W, Steiger J, Strom TB: Administration of noncytolytic IL-10/Fc in murine models of lipopolysaccharide-induced septic shock and allogeneic islet transplantation. J Immunol 1995; 154:5590–5600.

    PubMed  CAS  Google Scholar 

  27. Vossen ACTM, Tibbe GJM, Benner R, Savelkoul HFJ: T-lymphocyte and cytokine-directed strategies for inhibiting skin allograft rejection in mice. Transplant Proc 1995;27:380–382.

    PubMed  CAS  Google Scholar 

  28. Maeda H, Takata M, Takahashi S, Ogoshi S, Fujimoto S: Adoptive transfer of a Th2-like cell line prolongs MHC class II antigen disparate skinallograft survival in the mouse. Int Immunol 1994;6:855–862.

    Article  PubMed  CAS  Google Scholar 

  29. Maliszewski CR, Morrisey PJ, Fanslow WC, Sato TA, Willis C, Davidcon B: Delayed allograft rejection in mice transgenic for a soluble from of the IL-4-receptor. Cell Immunol 1992;143:434–448.

    Article  PubMed  CAS  Google Scholar 

  30. Farslow WC, Clifford KN, Park LS, Rubin AS, Voice, RF, Beckmann MP, Widmer MB: Regulation of alloreactivity in vivo by IL-4 and the soluble IL-4 receptor. J Immunol 1991;147:535–548.

    Google Scholar 

  31. Qin L, Chavin KD, Ding Y, Favaro JP, Woodward JE, Lin J, Tahara H, Robbins P, Shoked A, Ho DY, Sapolsky RM, Lotze MT, Bromberg JS: Multiple vectors effectively achieve gene transfer in amurine cardiac transplantation model. Immunosuppression with TGFβ1 or IL-10. Transplantation 1995;59:809–816.

    Article  PubMed  CAS  Google Scholar 

  32. Van Buskirk A, Wakely ME, Orosz CG: Transfusion of polarized Th2-like cell populations into scid mousecardiac allograft recipients results in acute allograft rejection. Transplantation 1996;62:229–238.

    Article  Google Scholar 

  33. Davies JD, O'Connor E, Hall D, Krahl T, Trotter J, Sarvelnick N: CD4+ CD45RB low-density cells from untreated mice preventacute allograft rejection. J Immunol 1999;163:5353–5357.

    PubMed  CAS  Google Scholar 

  34. Hao L, Wang Y, Gill RG, Lafferty K: Role of the L3T4+ T cell in allograft rejection. J Immunol 1987;139:4022.

    PubMed  CAS  Google Scholar 

  35. Shizuru JA, Gregory AK, Chao CTB, Fathman CG: Islet allograft survival after a single course of treatment of recipient with antibody to L3T4. Science 1987; 237–278.

  36. Lazarovits AI, Poppema S, Zhang Z, Khandaker M, Le Feuvre CE, Singhal SK, Garcia BM, Ogasa N, Jevnikar AM, White MJ, Singh G, Stiller CR, Zhong RZ: Prevention and reversal of renal allograft

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Author notes

  1. Joanna Davies

    Present address: Department of Immunology, IMM-23, The Scrippes Research Institute, 10550 N. Torrey Pimes Road, 92037, La Jolla, CA

Authors and Affiliations

  1. Department of Immunology, IMM-23, The Scrippes Research Institute, 10550 N. Torrey Pimes Road, 92037, La Jolla, CA

    Shon De Hall & Edda Roberts

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  1. Shon De Hall
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  2. Edda Roberts
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De Hall, S., Roberts, E. & Davies, J. Allograft rejection results from a failed attempt by the immune system to protect foreign tissue. Immunol Res 21, 177–183 (2000). https://doi.org/10.1385/IR:21:2-3:177

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