PDF herunterladen
Horm Metab Res 2010; 42(13): 912-917
DOI: 10.1055/s-0030-1268457
Review

© Georg Thieme Verlag KG Stuttgart · New York

Endocrine Organs Under the Control of the Immune System: Potential Implications for Cellular Therapies

B. Jacobs1 , 2 , [*] , C. Papewalis1 , [*] , M. Ehlers1 , M. Schott1
  • 1Endocrine Cancer Center, Department of Endocrinology, Diabetes and Rheumatology, University Hospital Düsseldorf, Düsseldorf, Germany
  • 2Department of Internal Medicine 5, Hemotology and Internal Oncology, University Hospital Erlangen, Erlangen, Germany
Weitere Informationen

Publikationsverlauf

received 11.10.2010

accepted 28.10.2010

Publikationsdatum:
03. Dezember 2010 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Within the last couple of years much knowledge has been gained in understanding the immune interactions in endocrine diseases including endocrine malignancies and autoimmune diseases. The major players within the innate immune system represent NK cells. This review describes that these cells directly lyse tumor cells and promote the activity of other cells of the immune system, including dendritic cells (DCs), macrophages, Th1 cells, and cytotoxic T-lymphocytes (CTLs). NK cells may also be involved in the initiation of autoimmunity as they may accumulate in target organs of certain autoimmune diseases. On the other hand, there are cells of the adaptive immune system including antigen-presenting DCs and T cells with helper and effector function, which are responsible for a directed immune response. Within this review, we present an overview on the role of all these cell populations in endocrine disease and the potential use of such cells for immunotherapy in different endocrine diseases and refer to experimental settings as well as clinical studies.

Key words

dendritic cells (DCs) - natural killer (NK) cells - cytotoxic T cells (CTLs) - adoptive cell therapy - autoimmune thyroiditis (AIT) - diabetes - graft-versus-host disease (GVHD)

References

  • 1 Yokoyama WM. Mistaken notions about natural killer cells.  Nat Immunol. 2008;  9 481-485
    Suche in Google Scholar
  • 2 Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells.  Nat Immunol. 2008;  9 503-510
    Suche in Google Scholar
  • 3 Cooper CL, Brady G, Bilia F, Iscove NN, Quesenberry PJ. Expression of the Id family helix-loop-helix regulators during growth and development in the hematopoietic system.  Blood. 1997;  89 3155-3165
    Suche in Google Scholar
  • 4 Wagtmann N, Rajagopalan S, Winter CC, Peruzzi M, Long EO. Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer.  Immunity. 1995;  3 801-809
    Suche in Google Scholar
  • 5 Bahram S, Inoko H, Shiina T, Radosavljevic M. MIC and other NKG2D ligands: from none to too many.  Curr Opin Immunol. 2005;  17 505-509
    Suche in Google Scholar
  • 6 Sivori S, Parolini S, Marcenaro E, Castriconi R, Pende D, Millo R, Moretta A. Involvement of natural cytotoxicity receptors in human natural killer cell-mediated lysis of neuroblastoma and glioblastoma cell lines.  J Neuroimmunol. 2000;  107 220-225
    Suche in Google Scholar
  • 7 Miller JS, Cooley S, Parham P, Farag SS, Verneris MR, McQueen KL, Guethlein LA, Trachtenberg EA, Haagenson M, Horowitz MM, Klein JP, Weisdorf DJ. Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT.  Blood. 2007;  109 5058-5061
    Suche in Google Scholar
  • 8 Klingemann H, Boissel L. Targeted cellular therapy with natural killer cells.  Horm Metab Res. 2008;  40 122-125
    Suche in Google Scholar
  • 9 Davies SM, Ruggieri L, DeFor T, Wagner JE, Weisdorf DJ, Miller JS, Velardi A, Blazar BR. Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants. Killer immunoglobulin-like receptor.  Blood. 2002;  100 3825-3827
    Suche in Google Scholar
  • 10 Cook MA, Milligan DW, Fegan CD, Darbyshire PJ, Mahendra P, Craddock CF, Moss PA, Briggs DC. The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia.  Blood. 2004;  103 1521-1526
    Suche in Google Scholar
  • 11 Beelen DW, Ottinger HD, Ferencik S, Elmaagacli AH, Peceny R, Trenschel R, Grosse-Wilde H. Genotypic inhibitory killer immunoglobulin-like receptor ligand incompatibility enhances the long-term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias.  Blood. 2005;  105 2594-2600
    Suche in Google Scholar
  • 12 Farag SS, Bacigalupo A, Eapen M, Hurley C, Dupont B, Caligiuri MA, Boudreau C, Nelson G, Oudshoorn M, van RJ, Velardi A, Maiers M, Setterholm M, Confer D, Posch PE, Anasetti C, Kamani N, Miller JS, Weisdorf D, Davies SM. The effect of KIR ligand incompatibility on the outcome of unrelated donor transplantation: a report from the center for international blood and marrow transplant research, the European blood and marrow transplant registry, and the Dutch registry.  Biol Blood Marrow Transplant. 2006;  12 876-884
    Suche in Google Scholar
  • 13 Larghero J, Rocha V, Porcher R, Filion A, Ternaux B, Lacassagne MN, Robin M, Peffault de LR, Devergie A, Biscay N, Ribaud P, Benbunan M, Gluckman E, Marolleau JP, Socie G. Association of bone marrow natural killer cell dose with neutrophil recovery and chronic graft-versus-host disease after HLA identical sibling bone marrow transplants.  Br J Haematol. 2007;  138 101-109
    Suche in Google Scholar
  • 14 Lister J, Rybka WB, Donnenberg AD, Magalhaes-Silverman M, Pincus SM, Bloom EJ, Elder EM, Ball ED, Whiteside TL. Autologous peripheral blood stem cell transplantation and adoptive immunotherapy with activated natural killer cells in the immediate posttransplant period.  Clin Cancer Res. 1995;  1 607-614
    Suche in Google Scholar
  • 15 Krause SW, Gastpar R, Andreesen R, Gross C, Ullrich H, Thonigs G, Pfister K, Multhoff G. Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase i trial.  Clin Cancer Res. 2004;  10 3699-3707
    Suche in Google Scholar
  • 16 Magalhaes-Silverman M, Donnenberg A, Lembersky B, Elder E, Lister J, Rybka W, Whiteside T, Ball E. Posttransplant adoptive immunotherapy with activated natural killer cells in patients with metastatic breast cancer.  J Immunother. 2000;  23 154-160
    Suche in Google Scholar
  • 17 Iliopoulou EG, Kountourakis P, Karamouzis MV, Doufexis D, Ardavanis A, Baxevanis CN, Rigatos G, Papamichail M, Perez SA. A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer.  Cancer Immunol Immunother. 2010;  59 1781-1789
    Suche in Google Scholar
  • 18 Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, Orchard PJ, Blazar BR, Wagner JE, Slungaard A, Weisdorf DJ, Okazaki IJ, McGlave PB. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer.  Blood. 2005;  105 3051-3057
    Suche in Google Scholar
  • 19 Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L, Ponzoni M, Rossini S, Mavilio F, Traversari C, Bordignon C. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia.  Science. 1997;  276 1719-1724
    Suche in Google Scholar
  • 20 Dalbeth N, Gundle R, Davies RJ, Lee YC, McMichael AJ, Callan MF. CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation.  J Immunol. 2004;  173 6418-6426
    Suche in Google Scholar
  • 21 Lu L, Ikizawa K, Hu D, Werneck MB, Wucherpfennig KW, Cantor H. Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway.  Immunity. 2007;  26 593-604
    Suche in Google Scholar
  • 22 Solerte SB, Precerutti S, Gazzaruso C, Locatelli E, Zamboni M, Schifino N, Bonacasa R, Rondanelli M, Taccani D, Ferrari E, Fioravanti M. Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto's thyroiditis: normalizing effect of dehydroepiandrosterone sulfate.  Eur J Endocrinol. 2005;  152 703-712
    Suche in Google Scholar
  • 23 Ciampolillo A, Guastamacchia E, Amati L, Magrone T, Munno I, Jirillo E, Triggiani V, Fallacara R, Tafaro E. Modifications of the immune responsiveness in patients with autoimmune thyroiditis: evidence for a systemic immune alteration.  Curr Pharm Des. 2003;  9 1946-1950
    Suche in Google Scholar
  • 24 Sack J, Baker Jr JR, Weetman AP, Wartofsky L, Burman KD. Thyrocyte specific killer cell activity is decreased in patients with thyroid carcinoma.  Cancer. 1987;  59 1914-1917
    Suche in Google Scholar
  • 25 Flodstrom M, Maday A, Balakrishna D, Cleary MM, Yoshimura A, Sarvetnick N. Target cell defense prevents the development of diabetes after viral infection.  Nat Immunol. 2002;  3 373-382
    Suche in Google Scholar
  • 26 Rodacki M, Svoren B, Butty V, Besse W, Laffel L, Benoist C, Mathis D. Altered natural killer cells in type 1 diabetic patients.  Diabetes. 2007;  56 177-185
    Suche in Google Scholar
  • 27 Ogasawara K, Hamerman JA, Hsin H, Chikuma S, Bour-Jordan H, Chen T, Pertel T, Carnaud C, Bluestone JA, Lanier LL. Impairment of NK cell function by NKG2D modulation in NOD mice.  Immunity. 2003;  18 41-51
    Suche in Google Scholar
  • 28 Ogasawara K, Hamerman JA, Ehrlich LR, Bour-Jordan H, Santamaria P, Bluestone JA, Lanier LL. NKG2D blockade prevents autoimmune diabetes in NOD mice.  Immunity. 2004;  20 757-767
    Suche in Google Scholar
  • 29 Gur C, Porgador A, Elboim M, Gazit R, Mizrahi S, Stern-Ginossar N, Achdout H, Ghadially H, Dor Y, Nir T, Doviner V, Hershkovitz O, Mendelson M, Naparstek Y, Mandelboim O. The activating receptor NKp46 is essential for the development of type 1 diabetes.  Nat Immunol. 2010;  11 121-128
    Suche in Google Scholar
  • 30 Lee IF, Qin H, Trudeau J, Dutz J, Tan R. Regulation of autoimmune diabetes by complete Freund's adjuvant is mediated by NK cells.  J Immunol. 2004;  172 937-942
    Suche in Google Scholar
  • 31 Lee IF, Qin H, Priatel JJ, Tan R. Critical role for IFN-gamma in natural killer cell-mediated protection from diabetes.  Eur J Immunol. 2008;  38 82-89
    Suche in Google Scholar
  • 32 Zhou R, Wei H, Tian Z. NK3-like NK cells are involved in protective effect of polyinosinic-polycytidylic acid on type 1 diabetes in nonobese diabetic mice.  J Immunol. 2007;  178 2141-2147
    Suche in Google Scholar
  • 33 Homann D, Jahreis A, Wolfe T, Hughes A, Coon B, van Stipdonk MJ, Prilliman KR, Schoenberger SP, von Herrath MG. CD40L blockade prevents autoimmune diabetes by induction of bitypic NK/DC regulatory cells.  Immunity. 2002;  16 403-415
    Suche in Google Scholar
  • 34 Schott M. Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers.  Endocr Relat Cancer. 2006;  13 779-795
    Suche in Google Scholar
  • 35 Oh JZ, Kedl RM. The Capacity To Induce Cross-Presentation Dictates the Success of a TLR7 Agonist-Conjugate Vaccine for Eliciting Cellular Immunity.  J Immunol. 2010;  185 4602-4608
    Suche in Google Scholar
  • 36 Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6.  Immunity. 2003;  19 225-234
    Suche in Google Scholar
  • 37 Amigorena S, Savina A. Intracellular mechanisms of antigen cross presentation in dendritic cells.  Curr Opin Immunol. 2010;  22 109-117
    Suche in Google Scholar
  • 38 Blanchard N, Shastri N. Cross-presentation of peptides from intracellular pathogens by MHC class I molecules.  Ann NY Acad Sci. 2010;  1183 237-250
    Suche in Google Scholar
  • 39 Lees JR, Farber DL. Generation, persistence and plasticity of CD4 T-cell memories.  Immunology. 2010;  130 463-470
    Suche in Google Scholar
  • 40 Woerly G, Roger N, Loiseau S, Dombrowicz D, Capron A, Capron M. Expression of CD28 and CD86 by human eosinophils and role in the secretion of type 1 cytokines (interleukin 2 and interferon gamma): inhibition by immunoglobulin a complexes.  J Exp Med. 1999;  190 487-495
    Suche in Google Scholar
  • 41 Dustin ML, Long EO. Cytotoxic immunological synapses.  Immunol Rev. 2010;  235 24-34
    Suche in Google Scholar
  • 42 Weigelin B, Friedl P. A three-dimensional organotypic assay to measure target cell killing by cytotoxic T lymphocytes.  Biochem Pharmacol. 2010;  80 2087-2091
    Suche in Google Scholar
  • 43 Janssen EM, Lemmens EE, Gour N, Reboulet RA, Green DR, Schoenberger SP, Pinkoski MJ. Distinct roles of cytolytic effector molecules for antigen-restricted killing by CTL in vivo.  Immunol Cell Biol. 2010;  88 761-765
    Suche in Google Scholar
  • 44 Halliday GM, Le S. Transforming growth factor-beta produced by progressor tumors inhibits, while IL-10 produced by regressor tumors enhances, Langerhans cell migration from skin.  Int Immunol. 2001;  13 1147-1154
    Suche in Google Scholar
  • 45 Oberg HH, Ly TT, Ussat S, Meyer T, Kabelitz D, Wesch D. Differential but direct abolishment of human regulatory T cell suppressive capacity by various TLR2 ligands.  J Immunol. 2010;  184 4733-4740
    Suche in Google Scholar
  • 46 Banchereau J, Ueno H, Dhodapkar M, Connolly J, Finholt JP, Klechevsky E, Blanck JP, Johnston DA, Palucka AK, Fay J. Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon.  J Immunother. 2005;  28 505-516
    Suche in Google Scholar
  • 47 Chen W, Rains N, Young D, Stubbs RS. Dendritic cell-based cancer immunotherapy: potential for treatment of colorectal cancer?.  J Gastroenterol Hepatol. 2000;  15 698-705
    Suche in Google Scholar
  • 48 Lodge PA, Jones LA, Bader RA, Murphy GP, Salgaller ML. Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a phase II clinical trial.  Cancer Res. 2000;  60 829-833
    Suche in Google Scholar
  • 49 Van Gool S, Maes W, Ardon H, Verschuere T, Van CS, De VS. Dendritic cell therapy of high-grade gliomas.  Brain Pathol. 2009;  19 694-712
    Suche in Google Scholar
  • 50 Papewalis C, Wuttke M, Jacobs B, Domberg J, Willenberg H, Baehring T, Cupisti K, Raffel A, Chao L, Fenk R, Seissler J, Scherbaum WA, Schott M. Dendritic cell vaccination induces tumor epitope-specific Th1 immune response in medullary thyroid carcinoma.  Horm Metab Res. 2008;  40 108-116
    Suche in Google Scholar
  • 51 Schott M, Feldkamp J, Schattenberg D, Krueger T, Dotzenrath C, Seissler J, Scherbaum WA. Induction of cellular immunity in a parathyroid carcinoma treated with tumor lysate-pulsed dendritic cells.  Eur J Endocrinol. 2000;  142 300-306
    Suche in Google Scholar
  • 52 Schott M, Feldkamp J, Lettmann M, Simon D, Scherbaum WA, Seissler J. Dendritic cell immunotherapy in a neuroendocrine pancreas carcinoma.  Clin Endocrinol (Oxf). 2001;  55 271-277
    Suche in Google Scholar
  • 53 Schott M, Feldkamp J, Klucken M, Kobbe G, Scherbaum WA, Seissler J. Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination.  Cancer Immunol Immunother. 2002;  51 663-668
    Suche in Google Scholar
  • 54 Schott M, Reincke M, Ortmann D, Bornstein SR. Immunotherapy: new strategies for the treatment of adrenocortical carcinoma.  Horm Metab Res. 2003;  35 451-453
    Suche in Google Scholar
  • 55 Stift A, Sachet M, Yagubian R, Bittermann C, Dubsky P, Brostjan C, Pfragner R, Niederle B, Jakesz R, Gnant M, Friedl J. Dendritic cell vaccination in medullary thyroid carcinoma.  Clin Cancer Res. 2004;  10 2944-2953
    Suche in Google Scholar
  • 56 Siena S, Di Nicola M, Bregni M, Mortarini R, Anichini A, Lombardi L, Ravagnani F, Parmiani G, Gianni AM. Massive ex vivo generation of functional dendritic cells from mobilized CD34+ blood progenitors for anticancer therapy.  Exp Hematol. 1995;  23 1463-1471
    Suche in Google Scholar
  • 57 Kim S, Kim HO, Kim HJ, Lee K, Kim HS. Generation of functionally mature dendritic cells from elutriated monocytes using polyinosinic: polycytidylic acid and soluble CD40 ligand for clinical application.  Clin Exp Immunol. 2008;  154 365-374
    Suche in Google Scholar
  • 58 Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.  J Exp Med. 1994;  179 1109-1118
    Suche in Google Scholar
  • 59 Berger TG, Feuerstein B, Strasser E, Hirsch U, Schreiner D, Schuler G, Schuler-Thurner B. Large-scale generation of mature monocyte-derived dendritic cells for clinical application in cell factories.  J Immunol Methods. 2002;  268 131-140
    Suche in Google Scholar
  • 60 Jacobs B, Wuttke M, Papewalis C, Seissler J, Schott M. Dendritic cell subtypes and in vitro generation of dendritic cells.  Horm Metab Res. 2008;  40 99-107
    Suche in Google Scholar
  • 61 Papewalis C, Jacobs B, Wuttke M, Ullrich E, Baehring T, Fenk R, Willenberg HS, Schinner S, Cohnen M, Seissler J, Zacharowski K, Scherbaum WA, Schott M. IFN-{alpha} Skews Monocytes into CD56+-Expressing Dendritic Cells with Potent Functional Activities In Vitro and In Vivo.  J Immunol. 2008;  180 1462-1470
    Suche in Google Scholar
  • 62 Papewalis C, Fassnacht M, Willenberg HS, Domberg J, Fenk R, Rohr UP, Schinner S, Bornstein SR, Scherbaum WA, Schott M. Dendritic cells as potential adjuvant for immunotherapy in adrenocortical carcinoma.  Clin Endocrinol (Oxf). 2006;  65 215-222
    Suche in Google Scholar
  • 63 Bachleitner-Hofmann T, Strohschneider M, Krieger P, Sachet M, Dubsky P, Hayden H, Schoppmann SF, Pfragner R, Gnant M, Friedl J, Stift A. Heat shock treatment of tumor lysate-pulsed dendritic cells enhances their capacity to elicit antitumor T cell responses against medullary thyroid carcinoma.  J Clin Endocrinol Metab. 2006;  91 4571-4577
    Suche in Google Scholar
  • 64 Bachleitner-Hofmann T, Friedl J, Hassler M, Hayden H, Dubsky P, Sachet M, Rieder E, Pfragner R, Brostjan C, Riss S, Niederle B, Gnant M, Stift A. Pilot trial of autologous dendritic cells loaded with tumor lysate(s) from allogeneic tumor cell lines in patients with metastatic medullary thyroid carcinoma.  Oncol Rep. 2009;  21 1585-1592
    Suche in Google Scholar
  • 65 Papewalis C, Jacobs B, Wuttke M, Schott M. Cellular therapies in endocrine diseases.  Exp Clin Endocrinol Diabetes. 2008;  116 (S 01) S33-S39
    Suche in Google Scholar
  • 66 Papewalis C, Kouatchoua C, Wuttke M, Jacobs B, Scherbaum WA, Schott M. Chromogranin a as potential tumour antigen in pheochromocytoma.  Horm Metab Res. 2009;  41 707-709
    Suche in Google Scholar
  • 67 Hinkmann C, Knerr I, Hahn EG, Lohmann T, Seifarth CC. Reduced frequency of peripheral plasmacytoid dendritic cells in type 1 diabetes.  Horm Metab Res. 2008;  40 767-771
    Suche in Google Scholar
  • 68 Clare-Salzler MJ, Brooks J, Chai A, Van Herle K, Anderson C. Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer.  J Clin Invest. 1992;  90 741-748
    Suche in Google Scholar
  • 69 Shinomiya M, Fazle Akbar SM, Shinomiya H, Onji M. Transfer of dendritic cells (DC) ex vivo stimulated with interferon-gamma (IFN-gamma) down-modulates autoimmune diabetes in non-obese diabetic (NOD) mice.  Clin Exp Immunol. 1999;  117 38-43
    Suche in Google Scholar
  • 70 Feili-Hariri M, Dong X, Alber SM, Watkins SC, Salter RD, Morel PA. Immunotherapy of NOD mice with bone marrow-derived dendritic cells.  Diabetes. 1999;  48 2300-2308
    Suche in Google Scholar
  • 71 Creusot RJ, Yaghoubi SS, Kodama K, Dang DN, Dang VH, Breckpot K, Thielemans K, Gambhir SS, Fathman CG. Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced to express IL-4 in NOD mice.  Clin Immunol. 2008;  127 176-187
    Suche in Google Scholar
  • 72 Haase C, Yu L, Eisenbarth G, Markholst H. Antigen-dependent immunotherapy of non-obese diabetic mice with immature dendritic cells.  Clin Exp Immunol. 2010;  160 331-339
    Suche in Google Scholar
  • 73 Morin J, Faideau B, Gagnerault MC, Lepault F, Boitard C, Boudaly S. Passive transfer of flt-3L-derived dendritic cells delays diabetes development in NOD mice and associates with early production of interleukin (IL)-4 and IL-10 in the spleen of recipient mice.  Clin Exp Immunol. 2003;  134 388-395
    Suche in Google Scholar
  • 74 Machen J, Harnaha J, Lakomy R, Styche A, Trucco M, Giannoukakis N. Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells.  J Immunol. 2004;  173 4331-4341
    Suche in Google Scholar
  • 75 Krueger T, Wohlrab U, Klucken M, Schott M, Seissler J. Autoantigen-specific protection of non-obese diabetic mice from cyclophosphamide-accelerated diabetes by vaccination with dendritic cells.  Diabetologia. 2003;  46 1357-1365
    Suche in Google Scholar
  • 76 Haase C, Yu L, Eisenbarth G, Markholst H. Antigen-dependent immunotherapy of non-obese diabetic mice with immature dendritic cells.  Clin Exp Immunol. 2010;  160 331-339
    Suche in Google Scholar
  • 77 Mukhopadhaya A, Hanafusa T, Jarchum I, Chen YG, Iwai Y, Serreze DV, Steinman RM, Tarbell KV, DiLorenzo TP. Selective delivery of beta cell antigen to dendritic cells in vivo leads to deletion and tolerance of autoreactive CD8+ T cells in NOD mice.  Proc Natl Acad Sci USA. 2008;  105 6374-6379
    Suche in Google Scholar
  • 78 Giannoukakis N, Phillips B, Trucco M. Toward a cure for type 1 diabetes mellitus: diabetes-suppressive dendritic cells and beyond.  Pediatr Diabetes. 2008;  9 4-13
    Suche in Google Scholar
  • 79 Phillips B, Nylander K, Harnaha J, Machen J, Lakomy R, Styche A, Gillis K, Brown L, Lafreniere D, Gallo M, Knox J, Hogeland K, Trucco M, Giannoukakis N. A microsphere-based vaccine prevents and reverses new-onset autoimmune diabetes.  Diabetes. 2008;  57 1544-1555
    Suche in Google Scholar
  • 80 Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines.  Nat Med. 2004;  10 909-915
    Suche in Google Scholar
  • 81 Khammari A, Labarriere N, Vignard V, Nguyen JM, Pandolfino MC, Knol AC, Quereux G, Saiagh S, Brocard A, Jotereau F, Dreno B. Treatment of metastatic melanoma with autologous Melan-A/MART-1-specific cytotoxic T lymphocyte clones.  J Invest Dermatol. 2009;  129 2835-2842
    Suche in Google Scholar
  • 82 Pouw N, Treffers-Westerlaken E, Mondino A, Lamers C, Debets R. TCR gene-engineered T cell: limited T cell activation and combined use of IL-15 and IL-21 ensure minimal differentiation and maximal antigen-specificity.  Mol Immunol. 2010;  47 1411-1420
    Suche in Google Scholar
  • 83 Tan JT, Ernst B, Kieper WC, LeRoy E, Sprent J, Surh CD. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells.  J Exp Med. 2002;  195 1523-1532
    Suche in Google Scholar
  • 84 Kieper WC, Tan JT, Bondi-Boyd B, Gapin L, Sprent J, Ceredig R, Surh CD. Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of memory phenotype CD8+ T cells.  J Exp Med. 2002;  195 1533-1539
    Suche in Google Scholar
  • 85 Pardoll DM, Topalian SL. The role of CD4+ T cell responses in antitumor immunity.  Curr Opin Immunol. 1998;  10 588-594
    Suche in Google Scholar
  • 86 Antony PA, Piccirillo CA, Akpinarli A, Finkelstein SE, Speiss PJ, Surman DR, Palmer DC, Chan CC, Klebanoff CA, Overwijk WW, Rosenberg SA, Restifo NP. CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells.  J Immunol. 2005;  174 2591-2601
    Suche in Google Scholar
  • 87 Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2.  J Natl Cancer Inst. 1994;  86 1159-1166
    Suche in Google Scholar
  • 88 Wuttke M, Papewalis C, Jacobs B, Schott M. Identifying tumor antigens in endocrine malignancies.  Trends Endocrinol Metab. 2009;  20 122-129
    Suche in Google Scholar
  • 89 Mackensen A, Meidenbauer N, Vogl S, Laumer M, Berger J, Andreesen R. Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T cells for the treatment of patients with metastatic melanoma.  J Clin Oncol. 2006;  24 5060-5069
    Suche in Google Scholar
  • 90 To WC, Wood BG, Krauss JC, Strome M, Esclamado RM, Lavertu P, Dasko D, Kim JA, Plautz GE, Leff BE, Smith V, Sandstrom-Wakeling K, Shu S. Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck: a phase 1 study.  Arch Otolaryngol Head Neck Surg. 2000;  126 1225-1231
    Suche in Google Scholar
  • 91 Rapoport AP, Stadtmauer EA, Aqui N, Badros A, Cotte J, Chrisley L, Veloso E, Zheng Z, Westphal S, Mair R, Chi N, Ratterree B, Pochran MF, Natt S, Hinkle J, Sickles C, Sohal A, Ruehle K, Lynch C, Zhang L, Porter DL, Luger S, Guo C, Fang HB, Blackwelder W, Hankey K, Mann D, Edelman R, Frasch C, Levine BL, Cross A, June CH. Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer.  Nat Med. 2005;  11 1230-1237
    Suche in Google Scholar
  • 92 Ye Z, Shi M, Chan T, Sas S, Xu S, Xiang J. Engineered CD8+ cytotoxic T cells with fiber-modified adenovirus-mediated TNF-alpha gene transfection counteract immunosuppressive interleukin-10-secreting lung metastasis and solid tumors.  Cancer Gene Ther. 2007;  14 661-675
    Suche in Google Scholar
  • 93 Morgan RA, Dudley ME, Rosenberg SA. Adoptive cell therapy: genetic modification to redirect effector cell specificity.  Cancer J. 2010;  16 336-341
    Suche in Google Scholar
  • 94 Safinia N, Sagoo P, Lechler R, Lombardi G. Adoptive regulatory T cell therapy: challenges in clinical transplantation.  Curr Opin Organ Transplant. 2010;  15 427-434
    Suche in Google Scholar
  • 95 Bacchetta R, Gregori S, Serafini G, Sartirana C, Schulz U, Zino E, Tomiuk S, Jansen U, Ponzoni M, Paties CT, Fleischhauer K, Roncarolo MG. Molecular and functional characterization of alloantigen-specific anergic T-cells suitable for cell therapy.  Haematologica. 2010;  Aug. 16 [Epub ahead of print]
    Suche in Google Scholar
  • 96 Hilkens CM, Isaacs JD, Thomson AW. Development of dendritic cell-based immunotherapy for autoimmunity.  Int Rev Immunol. 2010;  29 156-183
    Suche in Google Scholar

1 These authors contributed equally to the manuscript.

Correspondence

Dr. M.Schott 

Endocrine Cancer Center

Department of Endocrinology,

Diabetes and Rheumatology

University Hospital D ü sseldorf

Moorenstr. 5

40225 Düsseldorf

Germany

Telefon: 49/211/8117 810

Fax: 49/211/8117 860

eMail: matthias.schott@med.uni-duesseldorf.de