Immune Responses in Transplantation: Application to Composite Tissue Allograft

ABSTRACT

After announcements of successful hand, larynx, knee, muscle, nerve, and, most recently, face transplantation, composite tissue allografts (CTAs) have been introduced into the armamentarium of plastic and reconstructive surgery. Because the microsurgical techniques required to perform CTA transplants are well established and used in daily practice by plastic surgeons, the immunologic aspects of transplantation remain of great interest to plastic surgeons. CTAs offer a unique potential for coverage of large multitissue defects; however, compared with the relatively homogenous tissue of solid organ transplants, the heterogenicity of tissue components of CTA may generate high immunologic responses. Although modern immunosuppressive agents significantly improve successful allograft acceptance, chronic allograft rejection as well as immunosuppressive drug toxicity remain major problems in the clinical practice of transplantation. The major goal of transplantation immunology is to develop tolerance to allograft transplants and long-term drug-free survival. Several experimental protocols have been designed to develop tolerance; however, none of them have been proved to induce tolerance in clinical transplantation. This review outlines the mechanisms of allograft acceptance and rejection and describes the barriers to transplantation tolerance based on our current knowledge as it applies to solid organs and CTA transplants. The review also describes innovative immunosuppressive protocols.

KEYWORDS

Composite tissue allograft - immune response - immunosuppression

REFERENCES

• 1 Dubernard J M, Owen E, Herzberg G et al.. Human hand allograft: report on first 6 months.  Lancet. 1999;  353 1315-1320
• 2 Lanzetta M, Petruzzo P, Dubernard J M et al.. Second Report (1998-2006) of the International Registry of Hand and Composite Tissue Transplantation.  Transplant Immunology. 2007;  18 1-6
• 3 Strome M, Stein J, Esclamado R. Laryngeal transplantation and 40-month follow-up.  N Engl J Med. 2001;  344 1676-1679
• 4 Guimberteau J C, Baudet J, Panconi B, Boileau R, Potaux L. Human allotransplant of a digital flexion system vascularized on the ulnar pedicle: a preliminary report and 1-year follow-up of two cases.  Plast Reconstr Surg. 1992;  89 1135-1147
• 5 Mackinnon S E, Doolabh V B, Novak C B, Trulock E P. Clinical outcome following nerve allograft transplantation.  Plast Reconstr Surg. 2001;  107 1419-1429
• 6 Levi D M, Tzakis A, Kato T et al.. Transplantation of the abdominal wall.  Lancet. 2003;  361 2173-2176
• 7 Devauchelle B, Badet L, Lengele B et al.. First human face allograft: early report.  Lancet. 2006;  368 203-209
• 8 Lee W P, Yaremchuk M J, Pan Y C, Randolph M A, Tan C M, Weiland A J. Relative antigenicity of components of a vascularized limb allograft.  Plast Reconstr Surg. 1991;  87 401-411
• 9 Ulusal B G, Ulusal A E, Ozmen S, Zins J E, Siemionow M. A new composite facial and scalp transplantation model in the rat.  Plast Reconstr Surg. 2003;  112 1302-1311
• 10 Demir Y, Ozmen S, Klimczak A, Mukherjee A, Siemionow M. Tolerance induction in composite facial tissue allograft transplantation in the rat model.  Plast Reconstr Surg. 2004;  114 1790-1801
• 11 Siemionow M Z, Demir Y, Mukerjee A, Klimczak A. Development and maintenance of donor specific chimerism in semi-allogenic and fully MHC mismatched facial allograft transplants.  Transplantation. 2005;  79 558-567
• 12 Siemionow M, Izycki D, Zielinski M. Donor-specific tolerance in fully major histocompatibility complex-mismatched limb allograft transplants under an anti-alpha beta T-cell receptor monoclonal antibody and cyclosporine A protocol.  Transplantation. 2003;  76 1662-1668
• 13 Siemionow M, Izycki D, Ozer K, Ozmen S, Klimczak A. Role of thymus in operational tolerance induction in limb allograft transplant model.  Transplantation. 2006;  81 1568-1576
• 14 Hettiaratchy S, Randolph M A, Petit F, Lee W P, Butler P E. Composite tissue allotransplantation-a new era in plastic surgery?.  Br J Plast Surg. 2004;  57 381-391
• 15 Aw M M. Transplant immunology.  J Pediatr Surg. 2003;  38 1275-1280
• 16 Roitt I, Brostoff J, Male D. Immunolgy. 5th ed. London; Mosby International Ltd 1998
• 17 Krieger N R, Yin D P, Fathman C G. CD4 + but not CD8 + cells are essential for allorejection.  J Exp Med. 1996;  184 2013-2018
• 18 Sayegh M H, Turka L A. The role of T-cell costimulatory activation pathways in transplant rejection.  N Engl J Med. 1998;  338 1813-1821
• 19 Zhai Y, Ghobrial R M, Busuttil R W, Kupiec-Weglinski J W. Th1 and Th2 cytokines in organ transplantation: paradigm lost?.  Crit Rev Immunol. 1999;  19 155-172
• 20 Womer K L, Sayegh M H, Auchincloss Jr H. Involvement of the direct and indirect pathways of allorecognition in tolerance induction.  Philos Trans R Soc Lond B Biol Sci. 2001;  356 639-647
• 21 Cendales L C, Kirk A D, Moresi J M, Ruiz P, Kleiner D E. Composite tissue allotransplantation: classification of clinical acute skin rejection.  Transplantation. 2005;  80 1676-1680
• 22 Rocha P N, Plumb T J, Crowley S D, Coffman T M. Effector mechanisms in transplant rejection.  Immunol Rev. 2003;  196 51-64
• 23 Hancock W W, Gao W, Shemmeri N et al.. Immunopathogenesis of accelerated allograft rejection in sensitized recipients: humoral and nonhumoral mechanisms.  Transplantation. 2002;  73 1392-1397
• 24 Williams J M, Holzknecht Z E, Plummer T B et al.. Acute vascular rejection and accommodation: divergent outcomes of the humoral response to organ transplantation.  Transplantation. 2004;  78 1471-1478
• 25 Kanitakis J, Jullien D, Petruzzo P et al.. Clinicopathologic features of graft rejection of the first human hand allograft.  Transplantation. 2003;  76 688-693
• 26 Kanitakis J, Badet L, Petruzzo P et al.. First human face allotransplantation: monitoring of rejection with a pathlogical score assessing human composite tissue allograft rejection [abstract 967].  Transplantation. 2006;  82(Suppl 3) 392
• 27 Moll S, Pascual M. Humoral rejection of organ allografts.  Am J Transplant. 2005;  5 2611-2618
• 28 Petruzzo P, Badet L, Gazarian A et al.. Bilateral hand transplantation: six years after the first case.  Am J Transplant. 2006;  6 1718-1724
• 29 Cendales L C, Xu H, Bacher J et al.. Composite tissue allotransplantation: development of a preclinical model in nonhuman primates.  Transplantation. 2005;  80 1447-1454
• 30 Joosten S A, Sijpkens Y W, van Kooten C, Paul L C. Chronic renal allograft rejection: pathophysiologic considerations.  Kidney Int. 2005;  68 1-13
• 31 Womer K L, Stone J R, Murphy B, Chandraker A, Sayegh M H. Indirect allorecognition of donor class I and II major histocompatibility complex peptides promotes the development of transplant vasculopathy.  J Am Soc Nephrol. 2001;  12 2500-2506
• 32 Takada M, Nadeau K C, Hancock W W et al.. Effects of explosive brain death on cytokine activation of peripheral organs in the rat.  Transplantation. 1998;  65 1533-1542
• 33 Kuecuek O, Mantouvalou L, Klemz R et al.. Significant reduction of proinflammatory cytokines by treatment of the brain-dead donor.  Transplant Proc. 2005;  37 387-388
• 34 Takada M, Nadeau K C, Shaw G D, Marquette K A, Tilney N L. The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney. Inhibition by a soluble P-selectin ligand.  J Clin Invest. 1997;  99 2682-2690
• 35 Gorantla V S, Barker J H, Jones Jr J W et al.. Immunosuppressive agents in transplantation: mechanism of action and current anti-rejection strategies.  Microsurgery. 2000;  20 420-429
• 36 Fehr T, Sykes M. Tolerance induction in clinical transplantation.  Transpl Immunol. 2004;  13 117-130
• 37 Petruzzo P, Revillard J P, Kanitakis J et al.. First human double hand transplantation: efficacy of a conventional immunosuppressive protocol.  Clin Transplant. 2003;  17 455-460
• 38 Buell J F, Gross T G, Woodle E S. Malignancy after transplantation.  Transplantation. 2005;  80(2 Suppl) S254-S264
• 39 Cherikh W S, Kauffman H M, McBride M A et al.. Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival and patient survival after primary kidney transplantation.  Transplantation. 2003;  76 1289-1293