The importance of the indirect pathway of allorecognition in clinical transplantation

Current Opinion in Immunology

Volumn 20, Issue 5, 2008, Pages 568-574

  Gökmen, M Refik ^a   Lombardi, Giovanna ^a   Lechler, Robert I ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; HLA DR ANTIGEN; INTERLEUKIN 2 RECEPTOR ALPHA; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3;

ADAPTIVE IMMUNITY; ALLOIMMUNITY; ANTIGEN PRESENTING CELL; ANTIGEN SPECIFICITY; CD8+ T LYMPHOCYTE; CHRONIC GRAFT REJECTION; GRAFT DYSFUNCTION; GRAFT REJECTION; HEART TRANSPLANTATION; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; KIDNEY TRANSPLANTATION; LIVER TRANSPLANTATION; LUNG TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY COMPLEX; NONHUMAN; ORGAN TRANSPLANTATION; RECIPIENT; REGULATORY T LYMPHOCYTE; REVIEW; TRANSPLANTATION TOLERANCE;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; GRAFT REJECTION; HISTOCOMPATIBILITY ANTIGENS; HUMANS; IMMUNE TOLERANCE; ISOANTIGENS; T-LYMPHOCYTES, REGULATORY; TRANSPLANTATION IMMUNOLOGY; TRANSPLANTATION, HOMOLOGOUS;

EID: 50849112029     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2008.06.009     Document Type: Review

References (54)

1. Lechler R.I., and Batchelor J.R. Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med 155 (1982) 31-41
2. Herrera O.B., Golshayan D., Tibbott R., Salcido Ochoa F., James M.J., Marelli-Berg F.M., and Lechler R.I. A novel pathway of alloantigen presentation by dendritic cells. J Immunol 173 (2004) 4828-4837. This study showed that the acquisition by dendritic cells of intact MHC molecules from donor cells can elicit allospecific responses, demonstrating the semi-direct pathway of allorecognition.
3. Opelz G., and Dohler B. Effect of human leukocyte antigen compatibility on kidney graft survival: comparative analysis of two decades. Transplantation 84 (2007) 137-143
4. Ensminger S.M., Spriewald B.M., Witzke O., Pajaro O.E., Yacoub M.H., Morris P.J., Rose M.L., and Wood K.J. Indirect allorecognition can play an important role in the development of transplant arteriosclerosis. Transplantation 73 (2002) 279-286
5. Shirwan H., Mhoyan A., Yolcu E.S., Que X., and Ibrahim S. Chronic cardiac allograft rejection in a rat model disparate for one single class I MHC molecule is associated with indirect recognition by CD4(+) T cells. Transpl Immunol 11 (2003) 179-185
6. Yamada A., Laufer T.M., Gerth A.J., Chase C.M., Colvin R.B., Russell P.S., Sayegh M.H., and Auchincloss Jr. H. Further analysis of the T-cell subsets and pathways of murine cardiac allograft rejection. Am J Transplant 3 (2003) 23-27
7. Chalermskulrat W., Neuringer I.P., Brickey W.J., Felix N.J., Randell S.H., Ting J.P., and Aris R.M. Hierarchical contributions of allorecognition pathways in chronic lung rejection. Am J Respir Crit Care Med 167 (2003) 999-1007
8. Richards D.M., Dalheimer S.L., Ehst B.D., Vanasek T.L., Jenkins M.K., Hertz M.I., and Mueller D.L. Indirect minor histocompatibility antigen presentation by allograft recipient cells in the draining lymph node leads to the activation and clonal expansion of CD4+ T cells that cause obliterative airways disease. J Immunol 172 (2004) 3469-3479
9. Noorchashm H., Reed A.J., Rostami S.Y., Mozaffari R., Zekavat G., Koeberlein B., Caton A.J., and Naji A. B cell-mediated antigen presentation is required for the pathogenesis of acute cardiac allograft rejection. J Immunol 177 (2006) 7715-7722 This paper provides evidence for the role of B cells as antigen presenting cells acting through the indirect pathway.
10. Steele D.J., Laufer T.M., Smiley S.T., Ando Y., Grusby M.J., Glimcher L.H., and Auchincloss Jr. H. Two levels of help for B cell alloantibody production. J Exp Med 183 (1996) 699-703
11. Taylor A.L., Negus S.L., Negus M., Bolton E.M., Bradley J.A., and Pettigrew G.J. Pathways of helper CD4 T cell allorecognition in generating alloantibody and CD8 T cell alloimmunity. Transplantation 83 (2007) 931-937. This study demonstrates the importance of indirect allorecognition in generating humoral responses.
12. Mao Q., Terasaki P.I., Cai J., Briley K., Catrou P., Haisch C., and Rebellato L. Extremely high association between appearance of HLA antibodies and failure of kidney grafts in a five-year longitudinal study. Am J Transplant 7 (2007) 864-871
13. Sis B., Campbell P.M., Mueller T., Hunter C., Cockfield S.M., Cruz J., Meng C., Wishart D., Solez K., and Halloran P.F. Transplant glomerulopathy, late antibody-mediated rejection and the ABCD tetrad in kidney allograft biopsies for cause. Am J Transplant 7 (2007) 1743-1752
14. Baker R.J., Hernandez-Fuentes M.P., Brookes P.A., Chaudhry A.N., Cook H.T., and Lechler R.I. Loss of direct and maintenance of indirect alloresponses in renal allograft recipients: implications for the pathogenesis of chronic allograft nephropathy. J Immunol 167 (2001) 7199-7206
15. Poggio E.D., Roddy M., Riley J., Clemente M., Hricik D.E., Starling R., Young J.B., Gus B., Yamani M.H., and Heeger P.S. Analysis of immune markers in human cardiac allograft recipients and association with coronary artery vasculopathy. J Heart Lung Transplant 24 (2005) 1606-1613
16. Renna-Molajoni E., Cinti P., Orlandini A.M., Molajoni J., Cocciolo P.L., Evangelista B., Suciu-Foca N., and Cortesini R. Contribution of the direct and indirect allorecognition pathway to the rejection of liver allografts. Transplant Proc 30 (1998) 2138-2139
17. Stanford R.E., Ahmed S., Hodson M., Banner N.R., and Rose M.L. A role for indirect allorecognition in lung transplant recipients with obliterative bronchiolitis. Am J Transplant 3 (2003) 736-742
18. Bestard O., Nickel P., Cruzado J.M., Schoenemann C., Boenisch O., Sefrin A., Grinyo J.M., Volk H.D., and Reinke P. Circulating alloreactive T cells correlate with graft function in longstanding renal transplant recipients. J Am Soc Nephrol 19 (2008) 1419-1429
19. Valujskikh A., Lantz O., Celli S., Matzinger P., and Heeger P.S. Cross-primed CD8(+) T cells mediate graft rejection via a distinct effector pathway. Nat Immunol 3 (2002) 844-851. This study demonstrates that CD8 cells can also be activated via the indirect pathway as a result of cross-priming.
20. Valujskikh A., Zhang Q., and Heeger P.S. CD8 T cells specific for a donor-derived, self-restricted transplant antigen are nonpathogenic bystanders after vascularized heart transplantation in mice. J Immunol 176 (2006) 2190-2196
21. Grimm P.C., Nickerson P., Jeffery J., Savani R.C., Gough J., McKenna R.M., Stern E., and Rush D.N. Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal-allograft rejection. N Engl J Med 345 (2001) 93-97
22. Kapessidou Y., Habran C., Buonocore S., Flamand V., Barvais L., Goldman M., and Braun M.Y. The replacement of graft endothelium by recipient-type cells conditions allograft rejection mediated by indirect pathway CD4+ T cells. Transplantation 82 (2006) 582-591. This paper shows that the replacement of graft endothelium by recipient cells gives recipient cells with indirect allospecificity a vascular endothelial target for rejection.
23. Lechler R.I., Garden O.A., and Turka L.A. The complementary roles of deletion and regulation in transplantation tolerance. Nat Rev Immunol 3 (2003) 147-158
24. Tang Q., and Bluestone J.A. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol 9 (2008) 239-244. A comprehensive review of the multiple putative mechanisms of immune regulation by FoxP3+ T cells.
25. Rulifson I.C., Szot G.L., Palmer E., and Bluestone J.A. Inability to induce tolerance through direct antigen presentation. Am J Transplant 2 (2002) 510-519
26. Yamada A., Chandraker A., Laufer T.M., Gerth A.J., Sayegh M.H., and Auchincloss Jr. H. Recipient MHC class II expression is required to achieve long-term survival of murine cardiac allografts after costimulatory blockade. J Immunol 167 (2001) 5522-5526
27. Quezada S.A., Fuller B., Jarvinen L.Z., Gonzalez M., Blazar B.R., Rudensky A.Y., Strom T.B., and Noelle R.J. Mechanisms of donor-specific transfusion tolerance: preemptive induction of clonal T-cell exhaustion via indirect presentation. Blood 102 (2003) 1920-1926
28. Mirenda V., Berton I., Read J., Cook T., Smith J., Dorling A., and Lechler R.I. Modified dendritic cells coexpressing self and allogeneic major histocompatibility complex molecules: an efficient way to induce indirect pathway regulation. J Am Soc Nephrol 15 (2004) 987-997
29. Sanchez-Fueyo A., Domenig C.M., Mariat C., Alexopoulos S., Zheng X.X., and Strom T.B. Influence of direct and indirect allorecognition pathways on CD4+CD25+ regulatory T-cell function in transplantation. Transpl Int 20 (2007) 534-541. This study shows that regulatory T cell action is most potent when indirect presentation is the sole mechanism of allorecognition.
30. Sanchez-Fueyo A., Sandner S., Habicht A., Mariat C., Kenny J., Degauque N., Zheng X.X., Strom T.B., Turka L.A., and Sayegh M.H. Specificity of CD4+CD25+ regulatory T cell function in alloimmunity. J Immunol 176 (2006) 329-334
31. Toyokawa H., Nakao A., Bailey R.J., Nalesnik M.A., Kaizu T., Lemoine J.L., Ikeda A., Tomiyama K., Papworth G.D., Huang L., et al. Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation. Liver Transpl 14 (2008) 346-357
32. Ochando J.C., Homma C., Yang Y., Hidalgo A., Garin A., Tacke F., Angeli V., Li Y., Boros P., Ding Y., et al. Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts. Nat Immunol 7 (2006) 652-662
33. Ochando J.C., Krieger N.R., and Bromberg J.S. Direct versus indirect allorecognition: visualization of dendritic cell distribution and interactions during rejection and tolerization. Am J Transplant 6 (2006) 2488-2496. This study demonstrates the importance of the lymph node in the ongoing indirect presentation required for the generation of tolerance.
34. Callaghan C.J., Rouhani F.J., Negus M.C., Curry A.J., Bolton E.M., Bradley J.A., and Pettigrew G.J. Abrogation of antibody-mediated allograft rejection by regulatory CD4 T cells with indirect allospecificity. J Immunol 178 (2007) 2221-2228. This study shows that regulatory T cells with indirect allospecificity can abrogate antibody-mediated allograft rejection.
35. Verginis P., McLaughlin K.A., Wucherpfennig K.W., von Boehmer H., and Apostolou I. Induction of antigen-specific regulatory T cells in wild-type mice: visualization and targets of suppression. Proc Natl Acad Sci U S A 105 (2008) 3479-3484
36. Golshayan D., Jiang S., Tsang J., Garin M.I., Mottet C., and Lechler R.I. In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance. Blood 109 (2007) 827-835. This paper, together with references [37,38], demonstrates that alloantigen-specific regulatory T cells can be expanded in vitro and maintain the ability to suppress.
37. Jiang S., Tsang J., Game D.S., Stevenson S., Lombardi G., and Lechler R.I. Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect allospecificity: potential reagents to promote donor-specific transplantation tolerance. Transplantation 82 (2006) 1738-1743
38. Tsang J., Jiang S., Tanriver Y., Leung E., Lombardi G., and Lechler R.I. In vitro generation and characterisation of murine CD4+CD25+ regulatory T cells with indirect allospecificity. Int Immunopharmacol 6 (2006) 1883-1888
39. Bluestone J.A., Thomson A.W., Shevach E.M., and Weiner H.L. What does the future hold for cell-based tolerogenic therapy?. Nat Rev Immunol 7 (2007) 650-654
40. Game D.S., Hernandez-Fuentes M.P., Chaudhry A.N., and Lechler R.I. CD4+CD25+ regulatory T cells do not significantly contribute to direct pathway hyporesponsiveness in stable renal transplant patients. J Am Soc Nephrol 14 (2003) 1652-1661
41. Salama A.D., Najafian N., Clarkson M.R., Harmon W.E., and Sayegh M.H. Regulatory CD25+ T cells in human kidney transplant recipients. J Am Soc Nephrol 14 (2003) 1643-1651
42. Spadafora-Ferreira M., Caldas C., Fae K.C., Marrero I., Monteiro S.M., Lin-Wang H.T., Socorro-Silva A., Fonseca S.G., Fonseca J.A., Kalil J., et al. CD4+CD25+Foxp3+ indirect alloreactive T cells from renal transplant patients suppress both the direct and indirect pathways of allorecognition. Scand J Immunol 66 (2007) 352-361
43. Sewgobind V.D., van der Laan L.J., Klepper M., Ijzermans J.N., Tilanus H.W., Weimar W., and Baan C.C. Functional analysis of CD4(+) CD25(bright) T cells in kidney transplant patients: improving suppression of donor-directed responses after transplantation. Clin Transplant (2008)
44. Waanders M.M., Heidt S., Koekkoek K.M., Zoet Y.M., Doxiadis I.I., Amir A., Heemskerk M.H., Mulder A., Brand A., Roelen D.L., et al. Monitoring of indirect allorecognition: wishful thinking or solid data?. Tissue Antigens 71 (2008) 1-15. A useful and thought-provoking review of the different approaches to assaying the indirect alloresponse.
45. Carrodeguas L., Orosz C.G., Waldman W.J., Sedmak D.D., Adams P.W., and VanBuskirk A.M. Trans vivo analysis of human delayed-type hypersensitivity reactivity. Hum Immunol 60 (1999) 640-651
46. VanBuskirk A.M., Burlingham W.J., Jankowska-Gan E., Chin T., Kusaka S., Geissler F., Pelletier R.P., and Orosz C.G. Human allograft acceptance is associated with immune regulation. J Clin Invest 106 (2000) 145-155
47. Warnecke G., Chapman S.J., Bushell A., Hernandez-Fuentes M., and Wood K.J. Dependency of the trans vivo delayed type hypersensitivity response on the action of regulatory T cells: implications for monitoring transplant tolerance. Transplantation 84 (2007) 392-399
48. Smyth L.A., Afzali B., Tsang J., Lombardi G., and Lechler R.I. Intercellular transfer of MHC and immunological molecules: molecular mechanisms and biological significance. Am J Transplant 7 (2007) 1442-1449
49. Lee R.S., Grusby M.J., Glimcher L.H., Winn H.J., and Auchincloss Jr. H. Indirect recognition by helper cells can induce donor-specific cytotoxic T lymphocytes in vivo. J Exp Med 179 (1994) 865-872
50. Dolan B.P., Gibbs Jr. K.D., and Ostrand-Rosenberg S. Tumor-specific CD4+ T cells are activated by "cross-dressed" dendritic cells presenting peptide-MHC class II complexes acquired from cell-based cancer vaccines. J Immunol 176 (2006) 1447-1455
51. Montecalvo A., Shufesky W.J., Stolz D.B., Sullivan M.G., Wang Z., Divito S.J., Papworth G.D., Watkins S.C., Robbins P.D., Larregina A.T., et al. Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition. J Immunol 180 (2008) 3081-3090
52. Riond J., Elhmouzi J., Hudrisier D., and Gairin J.E. Capture of membrane components via trogocytosis occurs in vivo during both dendritic cells and target cells encounter by CD8(+) T cells. Scand J Immunol 66 (2007) 441-450
53. Morelli A.E., Larregina A.T., Shufesky W.J., Sullivan M.L., Stolz D.B., Papworth G.D., Zahorchak A.F., Logar A.J., Wang Z., Watkins S.C., et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104 (2004) 3257-3266
54. Peche H., Renaudin K., Beriou G., Merieau E., Amigorena S., and Cuturi M.C. Induction of tolerance by exosomes and short-term immunosuppression in a fully MHC-mismatched rat cardiac allograft model. Am J Transplant 6 (2006) 1541-1550