Advertisement
Review Article| Volume 28, ISSUE 3, P385-410, September 2008

Download started.

Ok

Microarrays: Monitoring for Transplant Tolerance and Mechanistic Insights

      With recent advances in immunology and a growing understanding of transplantation biology, the development of reliable assays that may be used for identification and prediction of the current state of an immune response (rejection and tolerance) are urgently needed to allow us to predict the development of immunologic graft injury, individualize immunosuppression, rationally minimize immunosuppressive drug toxicity, promote a better understanding of the mechanisms underlying stable graft acceptance, and aid in the design of tolerance-inducing clinical transplantation trials. Microarrays can provide nonbiased, simultaneous global expression patterns for more than 40,000 human genes across different experiments. High throughput microarray technology offers a means to study disease-specific transcriptional changes in tissue biopsy, peripheral blood, and biofluids.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Lechler R.I.
        • Sykes M.
        • Thomson A.W.
        • et al.
        Organ transplantation—how much of the promise has been realized?.
        Nat Med. 2005; 11: 605-613
        • Traum A.Z.
        • Kawai T.
        • Vacanti J.P.
        • et al.
        The need for tolerance in pediatric organ transplantation.
        Pediatrics. 2008; 121: 1258-1260
        • Cornell L.D.
        • Colvin R.B.
        Chronic allograft nephropathy.
        Curr Opin Nephrol Hypertens. 2005; 14: 229-234
        • Monaco A.P.
        Prospects and strategies for clinical tolerance.
        Transplant Proc. 2004; 36: 227-231
        • Girlanda R.
        • Kirk A.D.
        Frontiers in nephrology: immune tolerance to allografts in humans.
        J Am Soc Nephrol. 2007; 18: 2242-2251
        • Merrell K.T.
        • Benschop R.J.
        • Gauld S.B.
        • et al.
        Identification of anergic B cells within a wild-type repertoire.
        Immunity. 2006; 25: 953-962
        • Macian F.
        • Im S.H.
        • Garcia-Cozar F.J.
        • et al.
        T-cell anergy.
        Curr Opin Immunol. 2004; 16: 209-216
        • Lechler R.
        • Chai J.G.
        • Marelli-Berg F.
        • et al.
        The contributions of T-cell anergy to peripheral T-cell tolerance.
        Immunology. 2001; 103: 262-269
        • Najafian N.
        • Albin M.J.
        • Newell K.A.
        How can we measure immunologic tolerance in humans?.
        J Am Soc Nephrol. 2006; 17: 2652-2663
        • Trani J.
        • Moore D.J.
        • Jarrett B.P.
        • et al.
        CD25+ immunoregulatory CD4 T cells mediate acquired central transplantation tolerance.
        J Immunol. 2003; 170: 279-286
        • Jiang S.
        • Lechler R.I.
        Regulatory T cells in the control of transplantation tolerance and autoimmunity.
        Am J Transplant. 2003; 3: 516-524
        • Kurtz J.
        • Shaffer J.
        • Lie A.
        • et al.
        Mechanisms of early peripheral CD4 T-cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: evidence for anergy and deletion but not regulatory cells.
        Blood. 2004; 103: 4336-4343
        • Markees T.G.
        • Phillips N.E.
        • Gordon E.J.
        • et al.
        Long-term survival of skin allografts induced by donor splenocytes and anti-CD154 antibody in thymectomized mice requires CD4(+) T cells, interferon-gamma, and CTLA4.
        J Clin Invest. 1998; 101: 2446-2455
        • Thomson A.W.
        • Lu L.
        • Murase N.
        • et al.
        Microchimerism, dendritic cell progenitors and transplantation tolerance.
        Stem Cells. 1995; 13: 622-639
        • St Clair E.W.
        • Turka L.A.
        • Saxon A.
        • et al.
        New reagents on the horizon for immune tolerance.
        Annu Rev Med. 2007; 58: 329-346
        • Knechtle S.J.
        Development of tolerogenic strategies in the clinic.
        Philos Trans R Soc Lond, B, Biol Sci. 2005; 360: 1739-1746
        • Roussey-Kesler G.
        • Giral M.
        • Moreau A.
        • et al.
        Clinical operational tolerance after kidney transplantation.
        Am J Transplant. 2006; 6: 736-746
        • Zoller K.M.
        • Cho S.I.
        • Cohen J.J.
        • et al.
        Cessation of immunosuppressive therapy after successful transplantation: a national survey.
        Kidney Int. 1980; 18: 110-114
        • Ciancio G.
        • Miller J.
        • Garcia-Morales R.O.
        • et al.
        Six-year clinical effect of donor bone marrow infusions in renal transplant patients.
        Transplantation. 2001; 71: 827-835
        • Kawai T.
        • Cosimi A.B.
        • Spitzer T.R.
        • et al.
        HLA-mismatched renal transplantation without maintenance immunosuppression.
        N Engl J Med. 2008; 358: 353-361
        • Kawai T.
        • Cosimi A.B.
        • Colvin R.B.
        • et al.
        Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys.
        Transplantation. 1995; 59: 256-262
        • Spitzer T.R.
        • Delmonico F.
        • Tolkoff-Rubin N.
        • et al.
        Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism.
        Transplantation. 1999; 68: 480-484
        • Strober S.
        • Dhillon M.
        • Schubert M.
        • et al.
        Acquired immune tolerance to cadaveric renal allografts. A study of three patients treated with total lymphoid irradiation.
        N Engl J Med. 1989; 321: 28-33
        • Strober S.
        • Benike C.
        • Krishnaswamy S.
        • et al.
        Clinical transplantation tolerance twelve years after prospective withdrawal of immunosuppressive drugs: studies of chimerism and anti-donor reactivity.
        Transplantation. 2000; 69: 1549-1554
        • Kirk A.D.
        Induction immunosuppression.
        Transplantation. 2006; 82: 593-602
        • Gudmundsdottir H.
        • Turka L.A.
        T cell costimulatory blockade: new therapies for transplant rejection.
        J Am Soc Nephrol. 1999; 10: 1356-1365
        • Larsen C.P.
        • Knechtle S.J.
        • Adams A.
        • et al.
        A new look at blockade of T-cell costimulation: a therapeutic strategy for long-term maintenance immunosuppression.
        Am J Transplant. 2006; 6: 876-883
        • Alegre M.L.
        • Najafian N.
        Costimulatory molecules as targets for the induction of transplantation tolerance.
        Curr Mol Med. 2006; 6: 843-857
        • Harlan D.M.
        • Kirk A.D.
        The future of organ and tissue transplantation: can T-cell costimulatory pathway modifiers revolutionize the prevention of graft rejection?.
        JAMA. 1999; 282: 1076-1082
        • Scandling J.D.
        • Busque S.
        • Dejbakhsh-Jones S.
        • et al.
        Tolerance and chimerism after renal and hematopoietic-cell transplantation.
        N Engl J Med. 2008; 358: 362-368
        • VanBuskirk A.M.
        • Burlingham W.J.
        • Jankowska-Gan E.
        • et al.
        Human allograft acceptance is associated with immune regulation.
        J Clin Invest. 2000; 106: 145-155
        • Tanaka Y.
        • Ohdan H.
        • Onoe T.
        • et al.
        Low incidence of acute rejection after living-donor liver transplantation: immunologic analyses by mixed lymphocyte reaction using a carboxyfluorescein diacetate succinimidyl ester labeling technique.
        Transplantation. 2005; 79: 1262-1267
        • Li Y.
        • Koshiba T.
        • Yoshizawa A.
        • et al.
        Analyses of peripheral blood mononuclear cells in operational tolerance after pediatric living donor liver transplantation.
        Am J Transplant. 2004; 4: 2118-2125
        • Cortesini R.
        • Renna-Molajoni E.
        • Cinti P.
        • et al.
        Tailoring of immunosuppression in renal and liver allograft recipients displaying donor specific T-suppressor cells.
        Hum Immunol. 2002; 63: 1010-1018
        • Mazariegos G.V.
        • Zahorchak A.F.
        • Reyes J.
        • et al.
        Dendritic cell subset ratio in peripheral blood correlates with successful withdrawal of immunosuppression in liver transplant patients.
        Am J Transplant. 2003; 3: 689-696
        • Sumpter T.L.
        • Colvin B.L.
        • Wang Z.
        • et al.
        Plasmacytoid DC therapeutic potential is independent of IDO induction due to elevated DAP12 expression.
        Am J Transplant. 2008; 2: 203
        • Montagnoli C.
        • Perruccio K.
        • Bozza S.
        • et al.
        Provision of antifungal immunity and concomitant alloantigen tolerization by conditioned dendritic cells in experimental hematopoietic transplantation.
        Blood Cells Mol Dis. 2008; 40: 55-62
        • Ouabed A.
        • Hubert F.X.
        • Chabannes D.
        • et al.
        Differential control of T regulatory cell proliferation and suppressive activity by mature plasmacytoid versus conventional spleen dendritic cells.
        J Immunol. 2008; 180: 5862-5870
        • Zeevi A.
        • Britz J.A.
        • Bentlejewski C.A.
        • et al.
        Monitoring immune function during tacrolimus tapering in small bowel transplant recipients.
        Transpl Immunol. 2005; 15: 17-24
        • Braud C.
        • Baeten D.
        • Giral M.
        • et al.
        Immunosuppressive drug-free operational immune tolerance in human kidney transplant recipients: Part I. Blood gene expression statistical analysis.
        J Cell Biochem. 2008; 103: 1681-1692
        • Brouard S.
        • Mansfield E.
        • Braud C.
        • et al.
        Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance.
        Proc Natl Acad Sci U S A. 2007; 104: 15448-15453
        • Kawasaki M.
        • Iwasaki M.
        • Koshiba T.
        • et al.
        Gene expression profile analysis of the peripheral blood mononuclear cells from tolerant living-donor liver transplant recipients.
        Int Surg. 2007; 92: 276-286
        • Martinez-Llordella M.
        • Puig-Pey I.
        • Orlando G.
        • et al.
        Multiparameter immune profiling of operational tolerance in liver transplantation.
        Am J Transplant. 2007; 7: 309-319
        • Newell K.A.
        • Asare A.
        • Kirk A.D.
        • et al.
        A Unique B cell signature associated with operational tolerance.
        Am J Transplant. 2008; 2: 316
        • Hernandez Fuentes M.
        • Sawitzki B.
        Identification of immune tolerance in renal transplant.
        Am J Transplant. 2008; 2: 292
        • Li B.
        • Hartono C.
        • Ding R.
        • et al.
        Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine.
        N Engl J Med. 2001; 344: 947-954
        • Schaub S.
        • Rush D.
        • Wilkins J.
        • et al.
        Proteomic-based detection of urine proteins associated with acute renal allograft rejection.
        J Am Soc Nephrol. 2004; 15: 219-227
        • Newell K.A.
        • Larsen C.P.
        Tolerance assays: measuring the unknown.
        Transplantation. 2006; 81: 1503-1509
        • Hernandez-Fuentes M.P.
        • Warrens A.N.
        • Lechler R.I.
        Immunologic monitoring.
        Immunol Rev. 2003; 196: 247-264
        • Hernandez-Fuentes M.P.
        • Salama A.
        In vitro assays for immune monitoring in transplantation.
        Methods Mol Biol. 2006; 333: 269-290
        • Poggio E.D.
        • Clemente M.
        • Hricik D.E.
        • et al.
        Panel of reactive T cells as a measurement of primed cellular alloimmunity in kidney transplant candidates.
        J Am Soc Nephrol. 2006; 17: 564-572
        • Najafian N.
        • Salama A.D.
        • Fedoseyeva E.V.
        • et al.
        Enzyme-linked immunosorbent spot assay analysis of peripheral blood lymphocyte reactivity to donor HLA-DR peptides: potential novel assay for prediction of outcomes for renal transplant recipients.
        J Am Soc Nephrol. 2002; 13: 252-259
        • Sarwal M.
        • Chua M.S.
        • Kambham N.
        • et al.
        Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling.
        N Engl J Med. 2003; 349: 125-138
        • Hoffmann S.C.
        • Pearl J.P.
        • Blair P.J.
        • et al.
        Immune profiling: molecular monitoring in renal transplantation.
        Front Biosci. 2003; 8: e444-e462
        • Bloom D.D.
        • Hu H.
        • Fechner J.H.
        • et al.
        T-lymphocyte alloresponses of Campath-1H-treated kidney transplant patients.
        Transplantation. 2006; 81: 81-87
        • Muthukumar T.
        • Dadhania D.
        • Ding R.
        • et al.
        Messenger RNA for FOXP3 in the urine of renal-allograft recipients.
        N Engl J Med. 2005; 353: 2342-2351
        • Hu R.H.
        • Tsai M.K.
        • Lee P.H.
        Evaluation of cyclosporine C2 levels in long-term stable renal allograft recipients.
        Transplant Proc. 2004; 36: 2105-2107
        • Deng M.C.
        • Eisen H.J.
        • Mehra M.R.
        • et al.
        Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling.
        Am J Transplant. 2006; 6: 150-160
        • Vasconcellos L.M.
        • Schachter A.D.
        • Zheng X.X.
        • et al.
        Cytotoxic lymphocyte gene expression in peripheral blood leukocytes correlates with rejecting renal allografts.
        Transplantation. 1998; 66: 562-566
        • Sarwal M.M.
        • Jani A.
        • Chang S.
        • et al.
        Granulysin expression is a marker for acute rejection and steroid resistance in human renal transplantation.
        Hum Immunol. 2001; 62: 21-31
        • Ashton-Chess J.
        • Giral M.
        • Mengel M.
        • et al.
        Tribbles-1 as a novel biomarker of chronic antibody-mediated rejection.
        J Am Soc Nephrol. 2008; 19: 1116-1127
        • Mas V.
        • Maluf D.
        • Archer K.
        • et al.
        Establishing the molecular pathways involved in chronic allograft nephropathy for testing new noninvasive diagnostic markers.
        Transplantation. 2007; 83: 448-457
        • Hotchkiss H.
        • Chu T.T.
        • Hancock W.W.
        • et al.
        Differential expression of profibrotic and growth factors in chronic allograft nephropathy.
        Transplantation. 2006; 81: 342-349
        • Eikmans M.
        • Roos-van Groningen M.C.
        • Sijpkens Y.W.
        • et al.
        Expression of surfactant protein-C, S100A8, S100A9, and B cell markers in renal allografts: investigation of the prognostic value.
        J Am Soc Nephrol. 2005; 16: 3771-3786
        • Mansfield E.S.
        • Sarwal M.M.
        Arraying the orchestration of allograft pathology.
        Am J Transplant. 2004; 4: 853-862
        • Flechner S.M.
        • Kurian S.M.
        • Head S.R.
        • et al.
        Kidney transplant rejection and tissue injury by gene profiling of biopsies and peripheral blood lymphocytes.
        Am J Transplant. 2004; 4: 1475-1489
        • Scherer A.
        • Krause A.
        • Walker J.R.
        • et al.
        Early prognosis of the development of renal chronic allograft rejection by gene expression profiling of human protocol biopsies.
        Transplantation. 2003; 75: 1323-1330
        • Donauer J.
        • Rumberger B.
        • Klein M.
        • et al.
        Expression profiling on chronically rejected transplant kidneys.
        Transplantation. 2003; 76: 539-547
        • Akalin E.
        • Hendrix R.C.
        • Polavarapu R.G.
        • et al.
        Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology.
        Transplantation. 2001; 72: 948-953
        • Morgun A.
        • Shulzhenko N.
        • Perez-Diez A.
        • et al.
        Molecular profiling improves diagnoses of rejection and infection in transplanted organs.
        Circ Res. 2006; 98: e74-e83
        • Karason K.
        • Jernas M.
        • Hagg D.A.
        • et al.
        Evaluation of CXCL9 and CXCL10 as circulating biomarkers of human cardiac allograft rejection.
        BMC Cardiovasc Disord. 2006; 6: 29
        • Kulesh D.A.
        • Clive D.R.
        • Zarlenga D.S.
        • et al.
        Identification of interferon-modulated proliferation-related cDNA sequences.
        Proc Natl Acad Sci U S A. 1987; 84: 8453-8457
        • Schena M.
        • Shalon D.
        • Davis R.W.
        • et al.
        Quantitative monitoring of gene expression patterns with a complementary DNA microarray.
        Science. 1995; 270: 467-470
        • Lashkari D.A.
        • DeRisi J.L.
        • McCusker J.H.
        • et al.
        Yeast microarrays for genome wide parallel genetic and gene expression analysis.
        Proc Natl Acad Sci U S A. 1997; 94: 13057-13062
      1. Ying L, Sarwal M. In praise of arrays. Pediatr Nephrol, in press.

        • Lausted C.
        • Dahl T.
        • Warren C.
        • et al.
        POSaM: a fast, flexible, open-source, inkjet oligonucleotide synthesizer and microarrayer.
        Genome Biol. 2004; 5: R58
        • Cutler D.J.
        • Zwick M.E.
        • Carrasquillo M.M.
        • et al.
        High-throughput variation detection and genotyping using microarrays.
        Genome Res. 2001; 11: 1913-1925
        • Yan P.S.
        • Chen C.M.
        • Shi H.
        • et al.
        Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays.
        Cancer Res. 2001; 61: 8375-8380
        • Pollack J.R.
        • Perou C.M.
        • Alizadeh A.A.
        • et al.
        Genome-wide analysis of DNA copy-number changes using cDNA microarrays.
        Nat Genet. 1999; 23: 41-46
        • Relogio A.
        • Ben-Dov C.
        • Baum M.
        • et al.
        Alternative splicing microarrays reveal functional expression of neuron-specific regulators in Hodgkin lymphoma cells.
        J Biol Chem. 2005; 280: 4779-4784
        • Wang D.
        • Coscoy L.
        • Zylberberg M.
        • et al.
        Microarray-based detection and genotyping of viral pathogens.
        Proc Natl Acad Sci U S A. 2002; 99: 15687-15692
        • Conejero-Goldberg C.
        • Wang E.
        • Yi C.
        • et al.
        Infectious pathogen detection arrays: viral detection in cell lines and postmortem brain tissue.
        Biotechniques. 2005; 39: 741-751
        • Ji R.
        • Cheng Y.
        • Yue J.
        • et al.
        MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation.
        Circ Res. 2007; 100: 1579-1588
        • Alizadeh A.A.
        • Eisen M.B.
        • Davis R.E.
        • et al.
        Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.
        Nature. 2000; 403: 503-511
        • Perou C.M.
        • Sorlie T.
        • Eisen M.B.
        • et al.
        Molecular portraits of human breast tumours.
        Nature. 2000; 406: 747-752
        • Brown F.G.
        • Nikolic-Paterson D.J.
        • Chadban S.J.
        • et al.
        Urine macrophage migration inhibitory factor concentrations as a diagnostic tool in human renal allograft rejection.
        Transplantation. 2001; 71: 1777-1783
        • Chua M.S.
        • Barry C.
        • Chen X.
        • et al.
        Molecular profiling of anemia in acute renal allograft rejection using DNA microarrays.
        Am J Transplant. 2003; 3: 17-22
        • Patil J.
        • Lande J.D.
        • Li N.
        • et al.
        Bronchoalveolar lavage cell gene expression in acute lung rejection: development of a diagnostic classifier.
        Transplantation. 2008; 85: 224-231
        • Lande J.D.
        • Patil J.
        • Li N.
        • et al.
        Novel insights into lung transplant rejection by microarray analysis.
        Proc Am Thorac Soc. 2007; 4: 44-51
        • Gimino V.J.
        • Lande J.D.
        • Berryman T.R.
        • et al.
        Gene expression profiling of bronchoalveolar lavage cells in acute lung rejection.
        Am J Respir Crit Care Med. 2003; 168: 1237-1242
        • Lu B.S.
        • Yu A.D.
        • Zhu X.
        • et al.
        Sequential gene expression profiling in lung transplant recipients with chronic rejection.
        Chest. 2006; 130: 847-854
        • Mehra M.R.
        • Uber P.A.
        • Walther D.
        • et al.
        Gene expression profiles and B-type natriuretic peptide elevation in heart transplantation: more than a hemodynamic marker.
        Circulation. 2006; 114: I21-I26
      2. Li L, Ying L, Naesens M, et al. Interference of globin genes with biomarker discovery for allograft rejection in peripheral blood samples. Physiol Genomics, in press.

        • Braud C.
        • Shivozhelezov V.
        • Giral M.
        • et al.
        Statistical and non statistical analysis of peripheral blood gene expression of operational tolerance and chronic rejection in human renal allograft recipients.
        Am J Transplant. 2008; 2: 331
        • Martinez-Llordella M.
        • Lozano J.J.
        Functional pathways involved in operational allograft tolerance.
        Am J Transplant. 2008; 2: 247
        • Sawitzki B.
        • Reinke P.
        • Volk H.D.
        • et al.
        Autoimmunity and transplantation: a meeting at the crossroads in Berlin.
        Nat Immunol. 2008; 9: 447-449
        • Whitney A.R.
        • Diehn M.
        • Popper S.J.
        • et al.
        Individuality and variation in gene expression patterns in human blood.
        Proc Natl Acad Sci U S A. 2003; 100: 1896-1901
        • Boldrick J.C.
        • Alizadeh A.A.
        • Diehn M.
        • et al.
        Stereotyped and specific gene expression programs in human innate immune responses to bacteria.
        Proc Natl Acad Sci U S A. 2002; 99: 972-977
        • Alizadeh A.A.
        • Staudt L.M.
        Genomic-scale gene expression profiling of normal and malignant immune cells.
        Curr Opin Immunol. 2000; 12: 219-225
        • Salama A.D.
        • Najafian N.
        • Clarkson M.R.
        • et al.
        Regulatory CD25+ T cells in human kidney transplant recipients.
        J Am Soc Nephrol. 2003; 14: 1643-1651
        • McHugh R.S.
        • Whitters M.J.
        • Piccirillo C.A.
        • et al.
        CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor.
        Immunity. 2002; 16: 311-323
        • Shimizu J.
        • Yamazaki S.
        • Takahashi T.
        • et al.
        Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance.
        Nat Immunol. 2002; 3: 135-142
        • Bruder D.
        • Probst-Kepper M.
        • Westendorf A.M.
        • et al.
        Frontline: Neuropilin-1: a surface marker of regulatory T cells.
        Eur J Immunol. 2004; 34: 623-630
        • Cobbold S.P.
        • Castejon R.
        • Adams E.
        • et al.
        Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants.
        J Immunol. 2004; 172: 6003-6010
        • Walunas T.L.
        • Lenschow D.J.
        • Bakker C.Y.
        • et al.
        CTLA-4 can function as a negative regulator of T cell activation.
        Immunity. 1994; 1: 405-413
        • Gavin M.
        • Rudensky A.
        Control of immune homeostasis by naturally arising regulatory CD4+ T cells.
        Curr Opin Immunol. 2003; 15: 690-696
        • Jeon M.S.
        • Atfield A.
        • Venuprasad K.
        • et al.
        Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction.
        Immunity. 2004; 21: 167-177
      3. Lechler RI. Defining the “fingerprint” of clinical transplantation tolerance. Presented at the 8th International Conference on New Trends in Immunosuppression and Immunotherapy. Berlin, Germany; 2008.

      4. Seyfert-Margolis V. New approaches to answer old questions. Presented at the 8th International Conference on New Trends in Immunosuppression and Immunotherapy. Berlin, Germany; 2008.

        • Hillion S.
        • Pallier A.
        • Giral M.
        • et al.
        Contrasted peripheral blood B cell profile in long-term kidney graft acceptance.
        Am J Transplant. 2008; 2: 390
        • Kitchens W.H.
        • Uehara S.
        • Chase C.M.
        • et al.
        The changing role of natural killer cells in solid organ rejection and tolerance.
        Transplantation. 2006; 81: 811-817
        • Beilke J.N.
        • Gill R.G.
        Frontiers in nephrology: the varied faces of natural killer cells in transplantation–contributions to both allograft immunity and tolerance.
        J Am Soc Nephrol. 2007; 18: 2262-2267
        • Beilke J.N.
        • Kuhl N.R.
        • Van Kaer L.
        • et al.
        NK cells promote islet allograft tolerance via a perforin-dependent mechanism.
        Nat Med. 2005; 11: 1059-1065
        • Yu G.
        • Xu X.
        • Vu M.D.
        • et al.
        NK cells promote transplant tolerance by killing donor antigen-presenting cells.
        J Exp Med. 2006; 203: 1851-1858
        • Goldstein D.R.
        • Thomas J.M.
        • Kirklin J.K.
        • et al.
        An essential role for natural killer cells in augmentation of allograft survival mediated by donor spleen cells.
        Transplantation. 2001; 72: 954-956
        • Heeger P.S.
        • Lalli P.N.
        • Lin F.
        • et al.
        Decay-accelerating factor modulates induction of T cell immunity.
        J Exp Med. 2005; 201: 1523-1530
        • Walker W.E.
        • Nasr I.W.
        • Camirand G.
        • et al.
        Absence of innate MyD88 signaling promotes inducible allograft acceptance.
        J Immunol. 2006; 177: 5307-5316
        • Codarri L.
        • Vallotton L.
        • Ciuffreda D.
        • et al.
        Expansion and tissue infiltration of an allospecific CD4+CD25+CD45RO+IL-7Ralphahigh cell population in solid organ transplant recipients.
        J Exp Med. 2007; 204: 1533-1541
        • Fu F.
        • Li Y.
        • Qian S.
        • et al.
        Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86-) prolong cardiac allograft survival in nonimmunosuppressed recipients.
        Transplantation. 1996; 62: 659-665
        • Lu L.
        • McCaslin D.
        • Starzl T.E.
        • et al.
        Bone marrow-derived dendritic cell progenitors (NLDC 145+, MHC class II+, B7-1dim, B7-2-) induce alloantigen-specific hyporesponsiveness in murine T lymphocytes.
        Transplantation. 1995; 60: 1539-1545
        • McCurry K.R.
        • Colvin B.L.
        • Zahorchak A.F.
        • et al.
        Regulatory dendritic cell therapy in organ transplantation.
        Transpl Int. 2006; 19: 525-538
        • Wang Q.
        • Zhang M.
        • Ding G.
        • et al.
        Anti-ICAM-1 antibody and CTLA-4Ig synergistically enhance immature dendritic cells to induce donor-specific immune tolerance in vivo.
        Immunol Lett. 2003; 90: 33-42
        • Kronenberg K.I.
        • Inoue S.
        • Hutchinson J.A.
        • et al.
        Macrophages driven to a novel state of activation can promote tolerance.
        Am J Transplant. 2008; 2: 203
        • Sawitzki B.
        • Bushell A.
        • Steger U.
        • et al.
        Identification of gene markers for the prediction of allograft rejection or permanent acceptance.
        Am J Transplant. 2007; 7: 1091-1102
        • Pascher A.
        • Neuhaus P.
        Biliary complications after deceased-donor orthotopic liver transplantation.
        J Hepatobiliary Pancreat Surg. 2006; 13: 487-496
        • Brazma A.
        • Hingamp P.
        • Quackenbush J.
        • et al.
        Minimum information about a microarray experiment (MIAME)-toward standards for microarray data.
        Nat Genet. 2001; 29: 365-371
        • Spellman P.T.
        • Miller M.
        • Stewart J.
        • et al.
        Design and implementation of microarray gene expression markup language (MAGE-ML).
        Genome Biol. 2002; 3 (RESEARCH0046.1-0046.9)
        • Weimar W.
        • Rischen-Vos J.
        • de Kuiper P.
        • et al.
        Tapering immunosuppression in recipients of living donor kidney transplants.
        Nephrol Dial Transplant. 2004; 19: iv61-iv63