New ways to separate Graft-versus-Host Disease and Graft-versus-Tumour effects after allogeneic haematopoietic stem cell transplantation

British Journal of Haematology

Volumn 160, Issue 2, 2013, Pages 133-145

  Kotsiou, Eleni ^a   Davies, Jeff K ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Graft versus host disease; Immunotherapy; Transplantation

Indexed keywords

AZACITIDINE; CALCINEURIN INHIBITOR; CD103 ANTIGEN; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR7; FINGOLIMOD; INTERLEUKIN 21; INTERLEUKIN 23; L SELECTIN; MARAVIROC; METHOTREXATE; PURINERGIC P2X7 RECEPTOR; RAPAMYCIN; TUMOR ANTIGEN; TUMOR NECROSIS FACTOR ALPHA;

ADOPTIVE TRANSFER; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANTIGEN PRESENTING CELL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CYTOKINE RELEASE; DENDRITIC CELL; DONOR LYMPHOCYTE INFUSION; EFFECTOR CELL; GRAFT VERSUS HOST REACTION; GRAFT VERSUS LEUKEMIA EFFECT; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTE HOMING; LYMPHOCYTE MIGRATION; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; REDUCED INTENSITY CONDITIONING; REGULATORY T LYMPHOCYTE; REVIEW;

ADAPTIVE IMMUNITY; ANIMALS; ANTIGENS, NEOPLASM; CELL MOVEMENT; CLINICAL TRIALS AS TOPIC; CYTOKINES; GRAFT ENHANCEMENT, IMMUNOLOGIC; GRAFT VS HOST DISEASE; GRAFT VS TUMOR EFFECT; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNITY, INNATE; IMMUNOSUPPRESSIVE AGENTS; INFLAMMATION; LYMPHOCYTE TRANSFUSION; MICE; MODELS, IMMUNOLOGICAL; ORGAN SPECIFICITY; T-LYMPHOCYTE SUBSETS; TRANSLATIONAL MEDICAL RESEARCH; TRANSPLANTATION CONDITIONING; TRANSPLANTATION, HOMOLOGOUS; VACCINATION;

EID: 84872258471     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.12115     Document Type: Review

References (109)

1. Albert, M.H., Liu, Y., Anasetti, C. & Yu, X.Z. (2005) Antigen-dependent suppression of alloresponses by Foxp3-induced regulatory T cells in transplantation. European Journal of Immunology, 35, 2598-2607.
2. Anderson, B.E., Taylor, P.A., McNiff, J.M., Jain, D., Demetris, A.J., Panoskaltsis-Mortari, A., Ager, A., Blazar, B.R., Shlomchik, W.D. & Shlomchik, M.J. (2008) Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells. Blood, 111, 5242-5251.
3. Antin, J.H., Weisdorf, D., Neuberg, D., Nicklow, R., Clouthier, S., Lee, S.J., Alyea, E., McGarigle, C., Blazar, B.R., Sonis, S., Soiffer, R.J. & Ferrara, J.L. (2002) Interleukin-1 blockade does not prevent acute graft-versus-host disease: results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation. Blood, 100, 3479-3482.
4. Bacigalupo, A., Van Lint, M.T., Occhini, D., Gualandi, F., Lamparelli, T., Sogno, G., Tedone, E., Frassoni, F., Tong, J. & Marmont, A.M. (1991) Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia. Blood, 77, 1423-1428.
5. Bailey-Bucktrout, S.L. & Bluestone, J.A. (2011) Regulatory T cells: stability revisited. Trends in Immunology, 32, 301-306.
6. Beilhack, A., Schulz, S., Baker, J., Beilhack, G.F., Nishimura, R., Baker, E.M., Landan, G., Herman, E.I., Butcher, E.C., Contag, C.H. & Negrin, R.S. (2008) Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs. Blood, 111, 2919-2928.
7. Billingham, R.E. (1966) The biology of graft-versus-host reactions. Harvey Lectures, 62, 21-78.
8. von Boehmer, H. (2005) Mechanisms of suppression by suppressor T cells. Nature Immunology, 6, 338-344.
9. Bogunia-Kubik, K., Duda, D., Suchnicki, K. & Lange, A. (2006) CCR5 deletion mutation and its association with the risk of developing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Haematologica, 91, 1628-1634.
10. Borsotti, C., Franklin, A.R., Lu, S.X., Kim, T.D., Smith, O.M., Suh, D., King, C.G., Chow, A., Liu, C., Alpdogan, O. & van Den Brink, M.R. (2007) Absence of donor T-cell-derived soluble TNF decreases graft-versus-host disease without impairing graft-versus-tumor activity. Blood, 110, 783-786.
11. Brunstein, C.G., Miller, J.S., Cao, Q., McKenna, D.H., Hippen, K.L., Curtsinger, J., Defor, T., Levine, B.L., June, C.H., Rubinstein, P., McGlave, P.B., Blazar, B.R. & Wagner, J.E. (2011) Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood, 117, 1061-1070.
12. Brusic, A. & Wu, C.J. (2012) Enhancing graft-versus-leukemia after transplant: the rise of anti-cancer vaccines. Frontiers in bioscience, 17, 635-655.
13. de Bueger, M., Bakker, A., Van Rood, J.J., Van der Woude, F. & Goulmy, E. (1992) Tissue distribution of human minor histocompatibility antigens. Ubiquitous versus restricted tissue distribution indicates heterogeneity among human cytotoxic T lymphocyte-defined non-MHC antigens. Journal of Immunology, 149, 1788-1794.
14. Campbell, D.J. & Butcher, E.C. (2002) Rapid acquisition of tissue-specific homing phenotypes by CD4(+) T cells activated in cutaneous or mucosal lymphoid tissues. Journal of Experimental Medicine, 195, 135-141.
15. Cao, T., Soto, A., Zhou, W., Wang, W., Eck, S., Walker, M., Harriman, G. & Li, L. (2009) Ex vivo expanded human CD4 + CD25 + Foxp3 + regulatory T cells prevent lethal xenogenic graft versus host disease (GVHD). Cellular Immunology, 258, 65-71.
16. Casucci, M., Bondanza, A., Falcone, L., Provasi, E., Magnani, Z. & Bonini, C. (2012) Genetic engineering of T cells for the immunotherapy of haematological malignancies. Tissue Antigens, 79, 4-14.
17. Chakrabarti, S., Mackinnon, S., Chopra, R., Kottaridis, P.D., Peggs, K., O'Gorman, P., Chakraverty, R., Marshall, T., Osman, H., Mahendra, P., Craddock, C., Waldmann, H., Hale, G., Fegan, C.D., Yong, K., Goldstone, A.H., Linch, D.C. & Milligan, D.W. (2002) High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood, 99, 4357-4363.
18. Chen, B.J., Cui, X., Sempowski, G.D., Liu, C. & Chao, N.J. (2004) Transfer of allogeneic CD62L- memory T cells without graft-versus-host disease. Blood, 103, 1534-1541.
19. Coghill, J.M., Carlson, M.J., Panoskaltsis-Mortari, A., West, M.L., Burgents, J.E., Blazar, B.R. & Serody, J.S. (2010) Separation of graft-versus-host disease from graft-versus-leukemia responses by targeting CC-chemokine receptor 7 on donor T cells. Blood, 115, 4914-4922.
20. Cooke, K.R., Gerbitz, A., Crawford, J.M., Teshima, T., Hill, G.R., Tesolin, A., Rossignol, D.P. & Ferrara, J.L. (2001) LPS antagonism reduces graft-versus-host disease and preserves graft-versus-leukemia activity after experimental bone marrow transplantation. The Journal of clinical investigation, 107, 1581-1589.
21. Couriel, D., Saliba, R., Hicks, K., Ippoliti, C., de Lima, M., Hosing, C., Khouri, I., Andersson, B., Gajewski, J., Donato, M., Anderlini, P., Kontoyiannis, D.P., Cohen, A., Martin, T., Giralt, S. & Champlin, R. (2004) Tumor necrosis factor-alpha blockade for the treatment of acute GVHD. Blood, 104, 649-654.
22. Das, R., Chen, X., Komorowski, R., Hessner, M.J. & Drobyski, W.R. (2009) Interleukin-23 secretion by donor antigen-presenting cells is critical for organ-specific pathology in graft-versus-host disease. Blood, 113, 2352-2362.
23. Das, R., Komorowski, R., Hessner, M.J., Subramanian, H., Huettner, C.S., Cua, D. & Drobyski, W.R. (2010) Blockade of interleukin-23 signaling results in targeted protection of the colon and allows for separation of graft-versus-host and graft-versus-leukemia responses. Blood, 115, 5249-5258.
24. Davies, J.K., Nadler, L.M. & Guinan, E.C. (2009) Expansion of allospecific regulatory T cells after anergized, mismatched bone marrow transplantation. Science Translational Medicine, 1, 1ra3.
25. Distler, E., Bloetz, A., Albrecht, J., Asdufan, S., Hohberger, A., Frey, M., Schnurer, E., Thomas, S., Theobald, M., Hartwig, U.F. & Herr, W. (2011) Alloreactive and leukemia-reactive T cells are preferentially derived from naive precursors in healthy donors: implications for immunotherapy with memory T cells. Haematologica, 96, 1024-1032.
26. Duerr, R.H., Taylor, K.D., Brant, S.R., Rioux, J.D., Silverberg, M.S., Daly, M.J., Steinhart, A.H., Abraham, C., Regueiro, M., Griffiths, A., Dassopoulos, T., Bitton, A., Yang, H., Targan, S., Datta, L.W., Kistner, E.O., Schumm, L.P., Lee, A.T., Gregersen, P.K., Barmada, M.M., Rotter, J.I., Nicolae, D.L. & Cho, J.H. (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science, 314, 1461-1463.
27. Edinger, M., Hoffmann, P., Ermann, J., Drago, K., Fathman, C.G., Strober, S. & Negrin, R.S. (2003) CD4 + CD25 + regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nature Medicine, 9, 1144-1150.
28. El-Asady, R., Yuan, R., Liu, K., Wang, D., Gress, R.E., Lucas, P.J., Drachenberg, C.B. & Hadley, G.A. (2005) TGF-{beta}-dependent CD103 expression by CD8(+) T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease. Journal of Experimental Medicine, 201, 1647-1657.
29. Elmaagacli, A.H., Koldehoff, M., Landt, O. & Beelen, D.W. (2008) Relation of an interleukin-23 receptor gene polymorphism to graft-versus-host disease after hematopoietic-cell transplantation. Bone Marrow Transplantation, 41, 821-826.
30. Ferrara, J.L. & Reddy, P. (2006) Pathophysiology of graft-versus-host disease. Seminars in Hematology, 43, 3-10.
31. Ferrara, J.L., Cooke, K.R., Pan, L. & Krenger, W. (1996) The immunopathophysiology of acute graft-versus-host-disease. Stem Cells, 14, 473-489.
32. Fondi, C., Nozzoli, C., Benemei, S., Baroni, G., Saccardi, R., Guidi, S., Nicoletti, P., Bartolozzi, B., Pimpinelli, N., Santucci, M., Bosi, A. & Massi, D. (2009) Increase in FOXP3 + regulatory T cells in GVHD skin biopsies is associated with lower disease severity and treatment response. Biology of blood and marrow transplantation, 15, 938-947.
33. Foster, A.E., Marangolo, M., Sartor, M.M., Alexander, S.I., Hu, M., Bradstock, K.F. & Gottlieb, D.J. (2004) Human CD62L- memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion. Blood, 104, 2403-2409.
34. Godfrey, W.R., Ge, Y.G., Spoden, D.J., Levine, B.L., June, C.H., Blazar, B.R. & Porter, S.B. (2004) In vitro-expanded human CD4(+)CD25(+) T-regulatory cells can markedly inhibit allogeneic dendritic cell-stimulated MLR cultures. Blood, 104, 453-461.
35. Goodyear, O.C., Dennis, M., Jilani, N.Y., Loke, J., Siddique, S., Ryan, G., Nunnick, J., Khanum, R., Raghavan, M., Cook, M., Snowden, J.A., Griffiths, M., Russell, N., Yin, J., Crawley, C., Cook, G., Vyas, P., Moss, P., Malladi, R. & Craddock, C.F. (2012) Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood, 119, 3361-3369.
36. Goulmy, E., Termijtelen, A., Bradley, B.A. & van Rood, J.J. (1976) Alloimmunity to human H-Y. Lancet, 2, 1206.
37. Den Haan, J.M., Meadows, L.M., Wang, W., Pool, J., Blokland, E., Bishop, T.L., Reinhardus, C., Shabanowitz, J., Offringa, R., Hunt, D.F., Engelhard, V.H. & Goulmy, E. (1998) The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism. Science, 279, 1054-1057.
38. Hanash, A.M., Kappel, L.W., Yim, N.L., Nejat, R.A., Goldberg, G.L., Smith, O.M., Rao, U.K., Dykstra, L., Na, I.K., Holland, A.M., Dudakov, J.A., Liu, C., Murphy, G.F., Leonard, W.J., Heller, G. & Van Den Brink, M.R. (2011) Abrogation of donor T-cell IL-21 signaling leads to tissue-specific modulation of immunity and separation of GVHD from GVL. Blood, 118, 446-455.
39. Herve, P., Flesch, M., Tiberghien, P., Wijdenes, J., Racadot, E., Bordigoni, P., Plouvier, E., Stephan, J.L., Bourdeau, H. & Holler, E. (1992) Phase I-II trial of a monoclonal anti-tumor necrosis factor alpha antibody for the treatment of refractory severe acute graft-versus-host disease. Blood, 79, 3362-3368.
40. Hicheri, Y., Bouchekioua, A., Hamel, Y., Henry, A., Rouard, H., Pautas, C., Beaumont, J.L., Kuentz, M., Cordonnier, C., Cohen, J.L. & Maury, S. (2008) Donor regulatory T cells identified by FoxP3 expression but also by the membranous CD4+ CD127low/neg phenotype influence graft-versus-tumor effect after donor lymphocyte infusion. Journal of Immunotherapy, 31, 806-811.
41. Hill, G.R., Crawford, J.M., Cooke, K.R., Brinson, Y.S., Pan, L. & Ferrara, J.L. (1997) Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood, 90, 3204-3213.
42. Hill, G.R., Cooke, K.R., Teshima, T., Crawford, J.M., Keith, J.C. Jr, Brinson, Y.S., Bungard, D. & Ferrara, J.L. (1998) Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation. The Journal of clinical investigation, 102, 115-123.
43. Hippen, K.L., Merkel, S.C., Schirm, D.K., Sieben, C.M., Sumstad, D., Kadidlo, D.M., McKenna, D.H., Bromberg, J.S., Levine, B.L., Riley, J.L., June, C.H., Scheinberg, P., Douek, D.C., Miller, J.S., Wagner, J.E. & Blazar, B.R. (2011a) Massive ex vivo expansion of human natural regulatory T cells (T(regs)) with minimal loss of in vivo functional activity. Science Translational Medicine, 3, 83ra41.
44. Hippen, K.L., Merkel, S.C., Schirm, D.K., Nelson, C., Tennis, N.C., Riley, J.L., June, C.H., Miller, J.S., Wagner, J.E. & Blazar, B.R. (2011b) Generation and large-scale expansion of human inducible regulatory T cells that suppress graft-versus-host disease. American Journal of Transplantation, 11, 1148-1157.
45. Hippen, K.L., Bucher, C., Schirm, D.K., Bearl, A.M., Brender, T., Mink, K.A., Waggie, K.S., Peffault de Latour, R., Janin, A., Curtsinger, J.M., Dillon, S.R., Miller, J.S., Socie, G. & Blazar, B.R. (2012) Blocking IL-21 signaling ameliorates xenogeneic GVHD induced by human lymphocytes. Blood, 119, 619-628.
46. Hoffmann, P., Ermann, J., Edinger, M., Fathman, C.G. & Strober, S. (2002) Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. Journal of Experimental Medicine, 196, 389-399.
47. Hoffmann, P., Eder, R., Kunz-Schughart, L.A., Andreesen, R. & Edinger, M. (2004) Large-scale in vitro expansion of polyclonal human CD4(+)CD25high regulatory T cells. Blood, 104, 895-903.
48. Holler, E., Rogler, G., Brenmoehl, J., Hahn, J., Herfarth, H., Greinix, H., Dickinson, A.M., Socie, G., Wolff, D., Fischer, G., Jackson, G., Rocha, V., Steiner, B., Eissner, G., Marienhagen, J., Schoelmerich, J. & Andreesen, R. (2006) Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination. Blood, 107, 4189-4193.
49. Horowitz, M.M., Gale, R.P., Sondel, P.M., Goldman, J.M., Kersey, J., Kolb, H.J., Rimm, A.A., Ringden, O., Rozman, C., Speck, B., Truitt, R.L., Zwaan, F.E. & Bortin, M.M. (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood, 75, 555-562.
50. Di Ianni, M., Falzetti, F., Carotti, A., Terenzi, A., Castellino, F., Bonifacio, E., Del Papa, B., Zei, T., Ostini, R.I., Cecchini, D., Aloisi, T., Perruccio, K., Ruggeri, L., Balucani, C., Pierini, A., Sportoletti, P., Aristei, C., Falini, B., Reisner, Y., Velardi, A., Aversa, F. & Martelli, M.F. (2011) Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood, 117, 3921-3928.
51. Ibrahim, R.B., Abidi, M.H., Cronin, S.M., Lum, L.G., Al-Kadhimi, Z., Ratanatharathorn, V. & Uberti, J.P. (2009) Nonabsorbable corticosteroids use in the treatment of gastrointestinal graft-versus-host disease. Biology of blood and marrow transplantation, 15, 395-405.
52. Kim, Y.M., Sachs, T., Asavaroengchai, W., Bronson, R. & Sykes, M. (2003) Graft-versus-host disease can be separated from graft-versus-lymphoma effects by control of lymphocyte trafficking with FTY720. The Journal of clinical investigation, 111, 659-669.
53. Kim, T.D., Terwey, T.H., Zakrzewski, J.L., Suh, D., Kochman, A.A., Chen, M.E., King, C.G., Borsotti, C., Grubin, J., Smith, O.M., Heller, G., Liu, C., Murphy, G.F., Alpdogan, O. & Van Den Brink, M.R. (2008) Organ-derived dendritic cells have differential effects on alloreactive T cells. Blood, 111, 2929-2940.
54. Kolb, H.J., Mittermuller, J., Clemm, C., Holler, E., Ledderose, G., Brehm, G., Heim, M. & Wilmanns, W. (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood, 76, 2462-2465.
55. Koreth, J., Matsuoka, K., Kim, H.T., McDonough, S.M., Bindra, B., Alyea, E.P. III, Armand, P., Cutler, C., Ho, V.T., Treister, N.S., Bienfang, D.C., Prasad, S., Tzachanis, D., Joyce, R.M., Avigan, D.E., Antin, J.H., Ritz, J. & Soiffer, R.J. (2011) Interleukin-2 and regulatory T cells in graft-versus-host disease. New England Journal of Medicine, 365, 2055-2066.
56. Lau, J., Sartor, M., Bradstock, K.F., Vuckovic, S., Munster, D.J. & Hart, D.N. (2007) Activated circulating dendritic cells after hematopoietic stem cell transplantation predict acute graft-versus-host disease. Transplantation, 83, 839-846.
57. Lee, K.H., Park, S.S., Kim, I., Kim, J.H., Ra, E.K., Yoon, S.S., Hong, Y.C., Park, S. & Kim, B.K. (2007) P2X7 receptor polymorphism and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation. Haematologica, 92, 651-657.
58. Li, B., New, J.Y., Yap, E.H., Lu, J., Chan, S.H. & Hu, H. (2001) Blocking L-selectin and alpha4-integrin changes donor cell homing pattern and ameliorates murine acute graft versus host disease. European Journal of Immunology, 31, 617-624.
59. Liang, Y., Liu, C., Djeu, J.Y., Zhong, B., Peters, T., Scharffetter-Kochanek, K., Anasetti, C. & Yu, X.Z. (2008) Beta2 integrins separate graft-versus-host disease and graft-versus-leukemia effects. Blood, 111, 954-962.
60. Liu, W., Putnam, A.L., Xu-Yu, Z., Szot, G.L., Lee, M.R., Zhu, S., Gottlieb, P.A., Kapranov, P., Gingeras, T.R., de St, Fazekas., Groth, B., Clayberger, C., Soper, D.M., Ziegler, S.F. & Bluestone, J.A. (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. Journal of Experimental Medicine, 203, 1701-1711.
61. Liu, K., Anthony, B.A., Yearsly, M.M., Hamadani, M., Gaughan, A., Wang, J.J., Devine, S.M. & Hadley, G.A. (2011) CD103 deficiency prevents graft-versus-host disease but spares graft-versus-tumor effects mediated by alloreactive CD8 T cells. PLoS ONE, 6, e21968.
62. Lorenz, E., Schwartz, D.A., Martin, P.J., Gooley, T., Lin, M.T., Chien, J.W., Hansen, J.A. & Clark, J.G. (2001) Association of TLR4 mutations and the risk for acute GVHD after HLA-matched-sibling hematopoietic stem cell transplantation. Biology of blood and marrow transplantation, 7, 384-387.
63. Matthews, K., Lim, Z., Afzali, B., Pearce, L., Abdallah, A., Kordasti, S., Pagliuca, A., Lombardi, G., Madrigal, J.A., Mufti, G.J. & Barber, L.D. (2009) Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab. Haematologica, 94, 956-966.
64. Maury, S., Lemoine, F.M., Hicheri, Y., Rosenzwajg, M., Badoual, C., Cherai, M., Beaumont, J.L., Azar, N., Dhedin, N., Sirvent, A., Buzyn, A., Rubio, M.T., Vigouroux, S., Montagne, O., Bories, D., Roudot-Thoraval, F., Vernant, J.P., Cordonnier, C., Klatzmann, D. & Cohen, J.L. (2010) CD4 + CD25 + regulatory T cell depletion improves the graft-versus-tumor effect of donor lymphocytes after allogeneic hematopoietic stem cell transplantation. Science Translational Medicine, 2, 41ra52.
65. Mayor, N.P., Shaw, B.E., Hughes, D.A., Maldonado-Torres, H., Madrigal, J.A., Keshav, S. & Marsh, S.G. (2007) Single nucleotide polymorphisms in the NOD2/CARD15 gene are associated with an increased risk of relapse and death for patients with acute leukemia after hematopoietic stem-cell transplantation with unrelated donors. Journal of Clinical Oncology, 25, 4262-4269.
66. McClune, B.L. & Weisdorf, D.J. (2010) Reduced-intensity conditioning allogeneic stem cell transplantation for older adults: is it the standard of care? Current Opinion in Hematology, 17, 133-138.
67. Menning, A., Loddenkemper, C., Westendorf, A.M., Szilagyi, B., Buer, J., Siewert, C., Hamann, A. & Huehn, J. (2010) Retinoic acid-induced gut tropism improves the protective capacity of Treg in acute but not in chronic gut inflammation. European Journal of Immunology, 40, 2539-2548.
68. Merad, M., Hoffmann, P., Ranheim, E., Slaymaker, S., Manz, M.G., Lira, S.A., Charo, I., Cook, D.N., Weissman, I.L., Strober, S. & Engleman, E.G. (2004) Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease. Nature Medicine, 10, 510-517.
69. Miura, Y., Thoburn, C.J., Bright, E.C., Phelps, M.L., Shin, T., Matsui, E.C., Matsui, W.H., Arai, S., Fuchs, E.J., Vogelsang, G.B., Jones, R.J. & Hess, A.D. (2004) Association of Foxp3 regulatory gene expression with graft-versus-host disease. Blood, 104, 2187-2193.
70. Murai, M., Yoneyama, H., Ezaki, T., Suematsu, M., Terashima, Y., Harada, A., Hamada, H., Asakura, H., Ishikawa, H. & Matsushima, K. (2003) Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction. Nature Immunology, 4, 154-160.
71. Mutis, T., Gillespie, G., Schrama, E., Falkenburg, J.H., Moss, P. & Goulmy, E. (1999) Tetrameric HLA class I-minor histocompatibility antigen peptide complexes demonstrate minor histocompatibility antigen-specific cytotoxic T lymphocytes in patients with graft-versus-host disease. Nature Medicine, 5, 839-842.
72. New, J.Y., Li, B., Koh, W.P., Ng, H.K., Tan, S.Y., Yap, E.H., Chan, S.H. & Hu, H.Z. (2002) T cell infiltration and chemokine expression: relevance to the disease localization in murine graft-versus-host disease. Bone Marrow Transplantation, 29, 979-986.
73. Palendira, U., Chinn, R., Raza, W., Piper, K., Pratt, G., Machado, L., Bell, A., Khan, N., Hislop, A.D., Steyn, R., Rickinson, A.B., Buckley, C.D. & Moss, P. (2008) Selective accumulation of virus-specific CD8 + T cells with unique homing phenotype within the human bone marrow. Blood, 112, 3293-3302.
74. Palmer, L.A., Sale, G.E., Balogun, J.I., Li, D., Jones, D., Molldrem, J.J., Storb, R.F. & Ma, Q. (2010) Chemokine receptor CCR5 mediates alloimmune responses in graft-versus-host disease. Biology of blood and marrow transplantation, 16, 311-319.
75. Panoskaltsis-Mortari, A., Price, A., Hermanson, J.R., Taras, E., Lees, C., Serody, J.S. & Blazar, B.R. (2004) In vivo imaging of graft-versus-host-disease in mice. Blood, 103, 3590-3598.
76. Penack, O., Holler, E. & Van Den Brink, M.R. (2010) Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors. Blood, 115, 1865-1872.
77. Peters, J.H., Hilbrands, L.B., Koenen, H.J. & Joosten, I. (2008) Ex vivo generation of human alloantigen-specific regulatory T cells from CD4(pos)CD25(high) T cells for immunotherapy. PLoS ONE, 3, e2233.
78. Petrovic, A., Alpdogan, O., Willis, L.M., Eng, J.M., Greenberg, A.S., Kappel, B.J., Liu, C., Murphy, G.J., Heller, G. & Van Den Brink, M.R. (2004) LPAM (alpha 4 beta 7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease. Blood, 103, 1542-1547.
79. Ram, R., Gafter-Gvili, A., Yeshurun, M., Paul, M., Raanani, P. & Shpilberg, O. (2009) Prophylaxis regimens for GVHD: systematic review and meta-analysis. Bone Marrow Transplantation, 43, 643-653.
80. Reibke, R., Garbi, N., Ganss, R., Hammerling, G.J., Arnold, B. & Oelert, T. (2006) CD8 + regulatory T cells generated by neonatal recognition of peripheral self-antigen. Proceedings of the National Academy of Sciences, USA, 103, 15142-15147.
81. Reshef, R., Luger, S.M., Hexner, E.O., Loren, A.W., Frey, N.V., Nasta, S.D., Goldstein, S.C., Stadtmauer, E.A., Smith, J., Bailey, S., Mick, R., Heitjan, D.F., Emerson, S.G., Hoxie, J.A., Vonderheide, R.H. & Porter, D.L. (2012) Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. New England Journal of Medicine, 367, 135-145.
82. Rezvani, K., Mielke, S., Ahmadzadeh, M., Kilical, Y., Savani, B.N., Zeilah, J., Keyvanfar, K., Montero, A., Hensel, N., Kurlander, R. & Barrett, A.J. (2006) High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood, 108, 1291-1297.
83. Rezvani, K., Yong, A.S., Mielke, S., Savani, B.N., Musse, L., Superata, J., Jafarpour, B., Boss, C. & Barrett, A.J. (2008) Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood, 111, 236-242.
84. Rieger, K., Loddenkemper, C., Maul, J., Fietz, T., Wolff, D., Terpe, H., Steiner, B., Berg, E., Miehlke, S., Bornhauser, M., Schneider, T., Zeitz, M., Stein, H., Thiel, E., Duchmann, R. & Uharek, L. (2006) Mucosal FOXP3 + regulatory T cells are numerically deficient in acute and chronic GvHD. Blood, 107, 1717-1723.
85. Roddie, C. & Peggs, K.S. (2011) Donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation. Expert opinion on biological therapy, 11, 473-487.
86. Roncarolo, M.G., Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K. & Levings, M.K. (2006) Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunological Reviews, 212, 28-50.
87. Ruggeri, L., Capanni, M., Urbani, E., Perruccio, K., Shlomchik, W.D., Tosti, A., Posati, S., Rogaia, D., Frassoni, F., Aversa, F., Martelli, M.F. & Velardi, A. (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science, 295, 2097-2100.
88. Sackstein, R. (2006) A revision of Billingham's tenets: the central role of lymphocyte migration in acute graft-versus-host disease. Biology of blood and marrow transplantation, 12, 2-8.
89. Sagoo, P., Ali, N., Garg, G., Nestle, F.O., Lechler, R.I. & Lombardi, G. (2011) Human regulatory T cells with alloantigen specificity are more potent inhibitors of alloimmune skin graft damage than polyclonal regulatory T cells. Science Translational Medicine, 3, 83ra42.
90. Sakaguchi, S., Miyara, M., Costantino, C.M. & Hafler, D.A. (2010) FOXP3 + regulatory T cells in the human immune system. Nature Reviews Immunology, 10, 490-500.
91. Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M., Selby, W., Alexander, S.I., Nanan, R., Kelleher, A., de St, Fazekas. & Groth, B. (2006) Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. Journal of Experimental Medicine, 203, 1693-1700.
92. Serody, J.S., Burkett, S.E., Panoskaltsis-Mortari, A., Ng-Cashin, J., McMahon, E., Matsushima, G.K., Lira, S.A., Cook, D.N. & Blazar, B.R. (2000) T-lymphocyte production of macrophage inflammatory protein-1alpha is critical to the recruitment of CD8(+) T cells to the liver, lung, and spleen during graft-versus-host disease. Blood, 96, 2973-2980.
93. Shlomchik, W.D., Couzens, M.S., Tang, C.B., McNiff, J., Robert, M.E., Liu, J., Shlomchik, M.J. & Emerson, S.G. (1999) Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science, 285, 412-415.
94. Takashima, S., Kadowaki, M., Aoyama, K., Koyama, M., Oshima, T., Tomizuka, K., Akashi, K. & Teshima, T. (2011) The Wnt agonist R-spondin1 regulates systemic graft-versus-host disease by protecting intestinal stem cells. Journal of Experimental Medicine, 208, 285-294.
95. Taylor, P.A., Lees, C.J. & Blazar, B.R. (2002) The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood, 99, 3493-3499.
96. Terwey, T.H., Kim, T.D., Kochman, A.A., Hubbard, V.M., Lu, S., Zakrzewski, J.L., Ramirez-Montagut, T., Eng, J.M., Muriglan, S.J., Heller, G., Murphy, G.F., Liu, C., Budak-Alpdogan, T., Alpdogan, O. & Van Den Brink, M.R. (2005) CCR2 is required for CD8-induced graft-versus-host disease. Blood, 106, 3322-3330.
97. Teshima, T., Hill, G.R., Pan, L., Brinson, Y.S., Van Den Brink, M.R., Cooke, K.R. & Ferrara, J.L. (1999) IL-11 separates graft-versus-leukemia effects from graft-versus-host disease after bone marrow transplantation. The Journal of clinical investigation, 104, 317-325.
98. Ukena, S.N., Velaga, S., Geffers, R., Grosse, J., Baron, U., Buchholz, S., Stadler, M., Bruder, D., Ganser, A. & Franzke, A. (2011) Human regulatory T cells in allogeneic stem cell transplantation. Blood, 118, e82-e92.
99. Valcarcel, D., Martino, R., Caballero, D., Martin, J., Ferra, C., Nieto, J.B., Sampol, A., Bernal, M.T., Pinana, J.L., Vazquez, L., Ribera, J.M., Besalduch, J., Moraleda, J.M., Carrera, D., Brunet, M.S., Perez-Simon, J.A. & Sierra, J. (2008) Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. Journal of Clinical Oncology, 26, 577-584.
100. Veerapathran, A., Pidala, J., Beato, F., Yu, X.Z. & Anasetti, C. (2011) Ex vivo expansion of human Tregs specific for alloantigens presented directly or indirectly. Blood, 118, 5671-5680.
101. Waldman, E., Lu, S.X., Hubbard, V.M., Kochman, A.A., Eng, J.M., Terwey, T.H., Muriglan, S.J., Kim, T.D., Heller, G., Murphy, G.F., Liu, C., Alpdogan, O. & Van Den Brink, M.R. (2006) Absence of beta7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine. Blood, 107, 1703-1711.
102. Wang, X., Lu, L. & Jiang, S. (2011) Regulatory T cells: customizing for the clinic. Science Translational Medicine, 3, 83ps19.
103. Weaver, C.H., Clift, R.A., Deeg, H.J., Storb, R., Appelbaum, F.R., Bensinger, W., Doney, K., Hansen, J.A., Martin, P.O. & Sanders, J. (1994) Effect of graft-versus-host disease prophylaxis on relapse in patients transplanted for acute myeloid leukemia. Bone Marrow Transplantation, 14, 885-893.
104. Weiss, I.D., Shoham, H., Wald, O., Wald, H., Beider, K., Abraham, M., Barashi, N., Galun, E., Nagler, A. & Peled, A. (2011) Ccr5 deficiency regulates the proliferation and trafficking of natural killer cells under physiological conditions. Cytokine, 54, 249-257.
105. Whitelegg, A. & Barber, L.D. (2004) The structural basis of T-cell allorecognition. Tissue Antigens, 63, 101-108.
106. Wilhelm, K., Ganesan, J., Muller, T., Durr, C., Grimm, M., Beilhack, A., Krempl, C.D., Sorichter, S., Gerlach, U.V., Juttner, E., Zerweck, A., Gartner, F., Pellegatti, P., Di Virgilio, F., Ferrari, D., Kambham, N., Fisch, P., Finke, J., Idzko, M. & Zeiser, R. (2010) Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R. Nature Medicine, 16, 1434-1438.
107. Wilson, J., Cullup, H., Lourie, R., Sheng, Y., Palkova, A., Radford, K.J., Dickinson, A.M., Rice, A.M., Hart, D.N. & Munster, D.J. (2009) Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease. Journal of Experimental Medicine, 206, 387-398.
108. Wysocki, C.A., Burkett, S.B., Panoskaltsis-Mortari, A., Kirby, S.L., Luster, A.D., McKinnon, K., Blazar, B.R. & Serody, J.S. (2004) Differential roles for CCR5 expression on donor T cells during graft-versus-host disease based on pretransplant conditioning. Journal of Immunology, 173, 845-854.
109. Zorn, E., Kim, H.T., Lee, S.J., Floyd, B.H., Litsa, D., Arumugarajah, S., Bellucci, R., Alyea, E.P., Antin, J.H., Soiffer, R.J. & Ritz, J. (2005) Reduced frequency of FOXP3 + CD4 + CD25 + regulatory T cells in patients with chronic graft-versus-host disease. Blood, 106, 2903-2911.