H von Boehmer

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-kappaB and NFAT
    I Aifantis
    Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Nat Immunol 2:403-9. 2001
  2. ncbi request reprint Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene
    Fotini Gounari
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Nat Immunol 3:489-96. 2002
  3. pmc In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro
    Ludger Klein
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Smith 736, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:8886-91. 2003
  4. pmc Dynamics of suppressor T cells: in vivo veritas
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney St, Smith 736, Boston, MA 02115, USA
    J Exp Med 198:845-9. 2003
  5. ncbi request reprint Negative selection of the T-cell repertoire: where and when does it occur?
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Immunol Rev 209:284-9. 2006
  6. pmc T cell receptor-instructed alphabeta versus gammadelta lineage commitment revealed by single-cell analysis
    Taras Kreslavsky
    Laboratory of Lymphocyte Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 205:1173-86. 2008
  7. pmc The E delta enhancer controls the generation of CD4- CD8- alphabetaTCR-expressing T cells that can give rise to different lineages of alphabeta T cells
    Iannis Aifantis
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 203:1543-50. 2006
  8. pmc Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase
    Elmar Jaeckel
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 197:1635-44. 2003
  9. pmc Pre-TCRalpha and TCRalpha are not interchangeable partners of TCRbeta during T lymphocyte development
    Christine Borowski
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Smith Building, 1 Jimmy Fund Way, Boston, MA 02115, USA
    J Exp Med 199:607-15. 2004
  10. pmc Differential synergy of Notch and T cell receptor signaling determines alphabeta versus gammadelta lineage fate
    Annette I Garbe
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 203:1579-90. 2006

Research Grants

  1. pTa-controlled reporter to identify lymphoid precursor
    Harald von Boehmer; Fiscal Year: 2003
  2. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2007
  3. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2006
  4. MOLECULAR AND CELLULAR ANALYSIS OF PRE-TCR FUNCTION
    Harald von Boehmer; Fiscal Year: 2002
  5. MOLECULAR AND CELLULAR ANALYSIS OF PRE-TCR FUNCTION
    Harald von Boehmer; Fiscal Year: 2003
  6. Generation of antigen-specific regulation T cells
    Harald von Boehmer; Fiscal Year: 2007
  7. pTa-controlled reporter to identify lymphoid precursor
    Harald von Boehmer; Fiscal Year: 2007
  8. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2009
  9. Extrathymic T cell precursors: commitment and efficacy
    Harald von Boehmer; Fiscal Year: 2009
  10. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2010

Detail Information

Publications93

  1. ncbi request reprint Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-kappaB and NFAT
    I Aifantis
    Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Nat Immunol 2:403-9. 2001
    ..We show also that the biphasic nature of the observed pre-TCR-induced rise in cytosolic Ca2+ differentially modulates the activities of the transcription factors NF-kappaB and NFAT in developing T cells...
  2. ncbi request reprint Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene
    Fotini Gounari
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Nat Immunol 3:489-96. 2002
    ..Thus, the pTalpha reporter can be used to trace lymphopoiesis between CLPs and alphabeta T cells. The slower extinction of the hCD25 reporter compared to pTalpha enabled us to define points at which pTalpha(-) lineages branched off...
  3. pmc In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro
    Ludger Klein
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Smith 736, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:8886-91. 2003
    ..Our results reveal properties of regulatory T cells that were not predicted from in vitro studies...
  4. pmc Dynamics of suppressor T cells: in vivo veritas
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney St, Smith 736, Boston, MA 02115, USA
    J Exp Med 198:845-9. 2003
  5. ncbi request reprint Negative selection of the T-cell repertoire: where and when does it occur?
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Immunol Rev 209:284-9. 2006
    ....
  6. pmc T cell receptor-instructed alphabeta versus gammadelta lineage commitment revealed by single-cell analysis
    Taras Kreslavsky
    Laboratory of Lymphocyte Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 205:1173-86. 2008
    ....
  7. pmc The E delta enhancer controls the generation of CD4- CD8- alphabetaTCR-expressing T cells that can give rise to different lineages of alphabeta T cells
    Iannis Aifantis
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 203:1543-50. 2006
    ..Thus, alphabetaTCR expression by CD4- CD8- thymocytes not only represents a transgenic artifact but occurs under physiological conditions...
  8. pmc Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase
    Elmar Jaeckel
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 197:1635-44. 2003
    ..In spite of specific tolerance insulitis and diabetes occurred with normal kinetics indicating that GAD is not an essential autoantigen in the pathogenesis of diabetes...
  9. pmc Pre-TCRalpha and TCRalpha are not interchangeable partners of TCRbeta during T lymphocyte development
    Christine Borowski
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Smith Building, 1 Jimmy Fund Way, Boston, MA 02115, USA
    J Exp Med 199:607-15. 2004
    ..We conclude that features intrinsic to the pre-TCR, which are absent in TCRalpha, are essential for its unique function...
  10. pmc Differential synergy of Notch and T cell receptor signaling determines alphabeta versus gammadelta lineage fate
    Annette I Garbe
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 203:1579-90. 2006
    ....
  11. pmc In vivo instruction of suppressor commitment in naive T cells
    Irina Apostolou
    Dana Farber Cancer Institute, Harvard Medical School, 44 Binney St, Boston, MA 02115, USA
    J Exp Med 199:1401-8. 2004
    ....
  12. pmc Effective destruction of Fas-deficient insulin-producing beta cells in type 1 diabetes
    Irina Apostolou
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    J Exp Med 198:1103-6. 2003
    ..Here we show that the Fas-deficient mice develop autoimmune diabetes with slightly accelerated kinetics indicating that Fas-dependent apoptosis of beta cells is a dispensable mode of cell death in this disease...
  13. pmc Repression of tumor suppressor miR-451 is essential for NOTCH1-induced oncogenesis in T-ALL
    Xiaoyu Li
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    J Exp Med 208:663-75. 2011
    ..Thus, miR-451 and miR-709 function as potent suppressors of oncogenesis in NOTCH1-induced mouse T-ALL, and miR-451 influences MYC expression in human T-ALL bearing NOTCH1 mutations...
  14. pmc Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope
    Carolin Daniel
    Laboratory of Lymphocyte Biology, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Exp Med 208:1501-10. 2011
    ..In contrast, natural insulin epitopes are ineffective. Subimmunogenic vaccination with strongly agonistic insulin mimetopes might represent a novel strategy to prevent T1D in humans at risk for the disease...
  15. pmc Smad3 binding to the foxp3 enhancer is dispensable for the development of regulatory T cells with the exception of the gut
    Susan M Schlenner
    Laboratory of Lymphocyte Biology, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Exp Med 209:1529-35. 2012
    ..We show that binding of Smad3 to the foxp3 enhancer is dispensable for T reg cell development in newborn and adult mice with the exception of the gut...
  16. pmc Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes
    Taras Kreslavsky
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute and 2 Program in Cellular and Molecular Medicine, Children s Hospital, and Immune Disease Institute, Harvard Medical School, Boston, MA 02115
    J Exp Med 210:1911-8. 2013
    ..No evidence could be obtained for antigen-induced TCR editing, whereas replacement of the transgenic TCRα chain by ongoing gene rearrangement occurred in some cells irrespective of the presence or absence of self-antigen. ..
  17. doi request reprint Therapeutic opportunities for manipulating T(Reg) cells in autoimmunity and cancer
    Harald von Boehmer
    Laboratory of Lymphocyte Biology, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nat Rev Drug Discov 12:51-63. 2013
    ....
  18. pmc The manipulation of immunity. Conference on from allergy to cancer: new perspectives for therapeutic vaccination
    Harald von Boehmer
    Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    EMBO Rep 5:765-70. 2004
  19. doi request reprint Checkpoints in lymphocyte development and autoimmune disease
    Harald von Boehmer
    Harvard Medical School and Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Nat Immunol 11:14-20. 2010
    ..Here we discuss several scenarios in which failures at developmental checkpoints result in autoimmunity...
  20. doi request reprint Positive and negative selection in Basel
    Harald von Boehmer
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 9:571-3. 2008
  21. pmc Oral tolerance: is it all retinoic acid?
    Harald von Boehmer
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 204:1737-9. 2007
    ..These results reveal new tolerance mechanisms that will aid the use of T reg cells in the clinic...
  22. ncbi request reprint Mechanisms of suppression by suppressor T cells
    Harald von Boehmer
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 6:338-44. 2005
    ....
  23. doi request reprint Central tolerance: essential for preventing autoimmune disease?
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Eur J Immunol 39:2313-6. 2009
    ....
  24. ncbi request reprint Immunology. Thoracic thymus, exclusive no longer
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Science 312:206-7. 2006
  25. ncbi request reprint Shaping the T cell repertoire
    Harald von Boehmer
    Havard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Immunol 176:3-4. 2006
  26. pmc Can studies of tolerance ever lead to therapy?
    H von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115 USA
    Ann Rheum Dis 65:iii41-3. 2006
    ..However, more work is needed before these findings can be safely translated into better targeted therapy and prevention of unwanted immune responses in clinical settings...
  27. pmc Mechanisms of self-nonself discrimination and possible clinical relevance
    Carolin Daniel
    Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Smith 736, Boston, MA 02115, USA
    Immunotherapy 1:631-44. 2009
    ..These molecular mechanisms should enable investigators to develop clinical protocols aiming at the specific prevention of unwanted immune responses, thereby replacing indiscriminate immunosuppression that often has fatal consequences...
  28. ncbi request reprint Unique features of the pre-T-cell receptor alpha-chain: not just a surrogate
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Nat Rev Immunol 5:571-7. 2005
    ..As described here, I consider that experimental evidence favours the latter view...
  29. ncbi request reprint T-cell lineage fate: instructed by receptor signals?
    H von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Curr Biol 10:R642-5. 2000
    ..Recent studies have shown that different T-cell receptor signals can affect CD4 or CD8 lineage choice. Thus, all the ingredients for instructive mechanisms of lineage fate are in place but other mechanisms cannot be completely ruled out...
  30. ncbi request reprint Thymic selection revisited: how essential is it?
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Immunol Rev 191:62-78. 2003
    ..Ectopically expressed organ-specific antigens contribute to thymic self-nonself discrimination, which represents an essential feature for the evolutionary fitness of mammalian species...
  31. ncbi request reprint Efficient thymic immigration of B220+ lymphoid-restricted bone marrow cells with T precursor potential
    Colin H Martin
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute Boston, Massachusetts, 02115, USA
    Nat Immunol 4:866-73. 2003
    ..Although the CLP-2 subset may represent the most differentiated population with T cell potential before commitment to the B cell lineage, other subsets of thymic immigrants capable of generating T cells may exist...
  32. ncbi request reprint Origin of regulatory T cells with known specificity for antigen
    Irina Apostolou
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Nat Immunol 3:756-63. 2002
    ..These data suggest that distinct pathways can be exploited to interfere with unwanted immune responses...
  33. ncbi request reprint Inducing and expanding regulatory T cell populations by foreign antigen
    Karsten Kretschmer
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nat Immunol 6:1219-27. 2005
    ..The extrathymic generation and proliferation of regulatory T cells may contribute to self-tolerance as well as the poor immunogenicity of tumors and may be exploited clinically to prevent or reverse unwanted immunity...
  34. ncbi request reprint Projection of an immunological self shadow within the thymus by the aire protein
    Mark S Anderson
    Section on Immunology and Immunogenetics, Joslin Diabetes Center Department of Medicine, Brigham and Women s Hospital Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Science 298:1395-401. 2002
    ..These findings highlight the importance of thymically imposed "central" tolerance in controlling autoimmunity...
  35. ncbi request reprint Somatic activation of beta-catenin bypasses pre-TCR signaling and TCR selection in thymocyte development
    F Gounari
    Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Nat Immunol 2:863-9. 2001
    ..Although active beta-catenin induced differentiation in the absence of TCRs, its action was associated with reduced proliferation and survival when compared to developmental changes induced by the pre-TCR or the alpha beta TCR...
  36. ncbi request reprint A critical role for the cytoplasmic tail of pTalpha in T lymphocyte development
    Iannis Aifantis
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Nat Immunol 3:483-8. 2002
    ..In contrast, the pTalpha juxtamembrane cysteine appeared to be dispensable for pre-TCR function...
  37. doi request reprint Direct presentation of antigen by lymph node stromal cells protects against CD8 T-cell-mediated intestinal autoimmunity
    Fay C Magnusson
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Gastroenterology 134:1028-37. 2008
    ..To determine the contribution of antigen-specific CD8 and CD4 T cells to the breakdown of the EGC network, we studied specific autoimmune targeting of an ectopic antigen expressed by EGCs...
  38. ncbi request reprint De novo production of antigen-specific suppressor cells in vivo
    Karsten Kretschmer
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nat Protoc 1:653-61. 2006
    ..The results show that delivery of T-cell receptor agonist ligands under subimmunogenic conditions represents a suitable approach for converting naive T cells into Treg...
  39. ncbi request reprint Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation
    Thorsten R Mempel
    CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Immunity 25:129-41. 2006
    ..Thus, T(reg) cells reversibly suppress CTL-mediated immunity by allowing acquisition of full effector potential but withholding the license to kill...
  40. ncbi request reprint Shaping the T cell repertoire
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Immunol 175:7067-8. 2005
  41. pmc Identification of a T lineage-committed progenitor in adult blood
    Andreas Krueger
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Immunity 26:105-16. 2007
    ..Thus, CTP represent T lineage-committed T cell precursors linking extrathymic with intrathymic lymphopoiesis in adult mice...
  42. ncbi request reprint The impact of CD4+CD25+ Treg on tumor specific CD8+ T cell cytotoxicity and cancer
    Khashayarsha Khazaie
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Semin Cancer Biol 16:124-36. 2006
    ....
  43. doi request reprint Regulatory T cells and antigen-specific tolerance
    Karsten Kretschmer
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Chem Immunol Allergy 94:8-15. 2008
    ..Thus, RA may interfere with the negative impact of costimulation on Treg conversion by interfering with the generation and/or function of AP-1...
  44. pmc TCR-inducible PLZF transcription factor required for innate phenotype of a subset of gammadelta T cells with restricted TCR diversity
    Taras Kreslavsky
    Laboratory of Lymphocyte Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Proc Natl Acad Sci U S A 106:12453-8. 2009
    ..Interestingly, expression of this TCR transgene led to the development of spontaneous dermatitis...
  45. pmc Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells
    Joel N H Stern
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 107:17280-5. 2010
    ..In addition, evidence for a CD4(+) T cell-mediated suppressor mechanism was obtained...
  46. pmc A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus
    M Lucila Scimone
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:7006-11. 2006
    ..Preferential thymus-tropism of CLP-2 correlated with higher chemokine receptor 9 expression than on other BM progenitors. Thus, CLP access to the thymus is controlled by a tissue-specific and subset-selective multistep adhesion cascade...
  47. pmc Phenotypic plasticity of T cell progenitors upon exposure to Notch ligands
    Andreas Krueger
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Exp Med 203:1977-84. 2006
    ....
  48. ncbi request reprint Making regulatory T cells with defined antigen specificity: role in autoimmunity and cancer
    Karsten Kretschmer
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Immunol Rev 212:163-9. 2006
    ..The precise mechanisms of suppression remain enigmatic, however, but may be further elucidated by the molecular analysis of suppressed versus non-suppressed T cells...
  49. doi request reprint Peripherally induced Treg: mode, stability, and role in specific tolerance
    Irina Apostolou
    Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    J Clin Immunol 28:619-24. 2008
    ....
  50. pmc c-Myc mediates pre-TCR-induced proliferation but not developmental progression
    Marei Dose
    Tufts New England Medical Center, 750 Washington St, Tufts NEMC no 5602, Boston, MA 02111, USA
    Blood 108:2669-77. 2006
    ....
  51. pmc Notch1-dependent lymphomagenesis is assisted by but does not essentially require pre-TCR signaling
    Antonio F Campese
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 108:305-10. 2006
    ..In contrast to previous studies, we found that disease development does not require pre-TCR but that it can be accelerated in Rag2(-/-) mice by transient mimicking of pre-TCR signals...
  52. pmc Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines
    Jens Nolting
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 206:2131-9. 2009
    ..Interleukin (IL)-6 strongly reduced RAR alpha expression levels such that a deficiency of the predominant RAR alpha 1 isoform leaves too little RAR alpha 2 for RA to inhibit the generation of Th17 cells in the presence of IL-6...
  53. pmc Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo
    Mei Ling Chen
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:419-24. 2005
    ....
  54. ncbi request reprint Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes
    Elmar Jaeckel
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nat Immunol 5:1028-35. 2004
    ..The results are consistent with the idea that the human IDDM2 locus controls susceptibility to type 1 diabetes by regulating intrathymic preproinsulin expression...
  55. pmc Genomic definition of multiple ex vivo regulatory T cell subphenotypes
    Markus Feuerer
    Department of Pathology, Harvard Medical School, and Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:5919-24. 2010
    ..Treg cells from the gut proved dissimilar to cells elicited by exposure to TGFbeta in vitro, but instead they resembled a CD103(+)Klrg1(+) subphenotype preferentially generated in response to lymphopenia...
  56. ncbi request reprint Selection of the T-cell repertoire: receptor-controlled checkpoints in T-cell development
    Harald von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts USA
    Adv Immunol 84:201-38. 2004
  57. doi request reprint Thymocyte selection: chemokine signaling is not only about the destination
    Michael Gleimer
    Laboratory of Lymphocyte Biology, Cancer Immunology and AIDS, Dana Farber Cancer Institute, Smith 736, Boston, MA 02115, USA
    Curr Biol 20:R316-8. 2010
    ..Two recent reports suggest that, during thymic beta-selection, the binding of the chemokine CXCL12 to the receptor CXCR4 on thymocytes provides not only directional but also developmental cues...
  58. pmc Enhancement of antigen-specific Treg vaccination in vivo
    Carolin Daniel
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:16246-51. 2010
    ....
  59. pmc Beta-catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation
    Zhuyan Guo
    Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, MA 02111, USA
    Blood 109:5463-72. 2007
    ..Thus, beta-catenin activation may provide a mechanism for the induction of T-cell-acute lymphoblastic leukemia (T-ALL) that does not depend on Notch activation...
  60. ncbi request reprint Requirement for cyclin D3 in lymphocyte development and T cell leukemias
    Ewa Sicinska
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 4:451-61. 2003
    ..These studies point to cyclin D3 as a potential target for therapeutic intervention in specific human malignancies...
  61. ncbi request reprint Peptide-based instruction of suppressor commitment in naïve T cells and dynamics of immunosuppression in vivo
    H von Boehmer
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Scand J Immunol 62:49-54. 2005
    ....
  62. ncbi request reprint Visualizing the course of antigen-specific CD8 and CD4 T cell responses to a growing tumor
    Ludger Klein
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Eur J Immunol 33:806-14. 2003
    ..In this scenario, adoptive immunotherapy rather than vaccination promises successful treatment...
  63. ncbi request reprint The TCR-HA, INS-HA transgenic model of autoimmune diabetes: limitations and expectations
    Irina Apostolou
    Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Smith 736, Boston, MA 02115, USA
    J Autoimmun 22:111-4. 2004
  64. pmc gammadeltaTCR ligands and lineage commitment
    Taras Kreslavsky
    Laboratory of Lymphocyte Biology, Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Smith 736, Boston, MA 02115, USA
    Semin Immunol 22:214-21. 2010
    ..Here we summarize evidence supporting a possible role for ligands in gammadelta T cell lineage commitment and the generation of gammadelta sublineages...
  65. pmc Alphabeta versus gammadelta lineage choice at the first TCR-controlled checkpoint
    Taras Kreslavsky
    Laboratory of Lymphocyte Biology, Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Curr Opin Immunol 22:185-92. 2010
    ..Recent experiments support the former view...
  66. pmc Kruppel-like factor KLF10 targets transforming growth factor-beta1 to regulate CD4(+)CD25(-) T cells and T regulatory cells
    Zhuoxiao Cao
    Department of Medicine, Cardiovascular Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 284:24914-24. 2009
    ..Thus, KLF10 is a critical regulator in the transcriptional network controlling TGF-beta1 in both CD4(+)CD25(-) T cells and T regs and plays an important role in regulating atherosclerotic lesion formation in mice...
  67. doi request reprint Notch 1 keeps pro-T cells on track
    Harald von Boehmer
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Immunity 30:5-7. 2009
    ..2009) report that Delta-like 4, acting on Notch 1, prevents pro-T cells from differentiating into dendritic cells and B cells. In addition, in the absence of Notch 1, B cells in the thymus arose from a cell-extrinsic pathway...
  68. ncbi request reprint TCR and Notch synergize in alphabeta versus gammadelta lineage choice
    Annette I Garbe
    Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Trends Immunol 28:124-31. 2007
    ..It remains to be determined whether TCR and/or Notch signals instruct or confirm predetermined lineage fate...
  69. ncbi request reprint Stabilization of beta-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia
    Fotini Gounari
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute Harvard Medical School, Boston, Massachusetts, MA 02115, USA
    Oncogene 21:4099-107. 2002
    ..Our observations indicate that beta-catenin stabilization is a crucial event for the initiation of PIN-like lesions, but induces squamous metaplasia rather than tumorigenesis in secretory epithelia other than the prostate...
  70. pmc Oncogenesis of T-ALL and nonmalignant consequences of overexpressing intracellular NOTCH1
    Xiaoyu Li
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 205:2851-61. 2008
    ..As judged by array-based comparative genomic hybridization (array CGH) and spectral karyotype (SKY) analysis, none of the tumors arise because of genomic instability...
  71. pmc Induction of antigen-specific regulatory T cells in wild-type mice: visualization and targets of suppression
    Panayotis Verginis
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:3479-84. 2008
    ..As a result, animals developed Treg-mediated long-term tolerance to all HY transplantation antigens, irrespective of whether they were recognized by CD4 or CD8 T cells, on skin or hematopoietic grafts from male donors...
  72. ncbi request reprint On the brink of becoming a T cell
    Christine Borowski
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Curr Opin Immunol 14:200-6. 2002
    ..Receptor editing and lineage commitment of alphabeta T cells still represent controversial topics that need further study...
  73. ncbi request reprint Type 1 diabetes: focus on prevention
    Harald von Boehmer
    Nat Med 10:783-4. 2004
  74. pmc Characterization of T cell differentiation in the murine gut
    Florence Lambolez
    Institut National de la Santé et de la Recherche Médicale INSERM U345, Institut Necker, rue de Vaugirard, 75730 Paris Cedex 15, France
    J Exp Med 195:437-49. 2002
    ..Finally, only 3% of CP cells were clearly involved in T cell differentiation, suggesting that these structures may have additional physiological roles in the gut...
  75. ncbi request reprint Neuropilin-1: a surface marker of regulatory T cells
    Dunja Bruder
    Eur J Immunol 34:623-30. 2004
    ..Thus, Nrp1 constitutes a useful surface marker to distinguish Treg cells from both naive and recently activated CD4+CD25+ non-regulatory T cells...
  76. pmc p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis
    Magali Fasseu
    Institut National de la Santé et de la Recherche Médicale INSERM U462, Institut Universitaire d Hematologie, Hopital Saint Louis, Paris, France
    Blood 110:2610-9. 2007
    ..We also show that the CD3epsilon-mediated signal transduction pathway is essential for this transformation process, since the TAL1xLMO1xCD3epsilon-deficient mice do not develop T-ALL for up to 1 year...
  77. ncbi request reprint Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation
    Maria Ciofani
    Department of Immunology, University of Toronto, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada
    Immunity 25:105-16. 2006
    ..Collectively, our findings demonstrate a differential, stage-specific requirement for Notch receptor-ligand interactions in the differentiation of alphabeta and gammadelta T cells from T cell progenitors...
  78. ncbi request reprint Positive selection by the pre-TCR yields mature CD8+ T cells
    Yuriko Ito
    Center for Immunology, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Immunol 169:4913-9. 2002
    ..The biased production of CD8(+) T cells via the pre-TCR might also support the potential involvement of signal strength in CD4/CD8 lineage commitment...
  79. pmc Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis
    Diana Bellavia
    Department of Experimental Medicine and Pathology, University La Sapienza, Viale Regina Elena 324, 00161 Roma, Italy
    Proc Natl Acad Sci U S A 99:3788-93. 2002
    ..Together, these results suggest that the combined expression of Notch3 and pTalpha sustains T cell leukemogenesis and may represent pathognomonic molecular features of human T-ALL...
  80. ncbi request reprint On the edge of autoimmunity: T-cell stimulation by steady-state dendritic cells prevents autoimmune diabetes
    Dunja Bruder
    Department of Mucosal Immunity, German Research Centre for Biotechnology, Mascheroder Weg 1, D 38124 Braunschweig, Germany
    Diabetes 54:3395-401. 2005
    ..Our results provide a basis for the development of novel strategies focusing on prevention rather than treatment of autoimmune diseases...
  81. pmc Foxp3 occupancy and regulation of key target genes during T-cell stimulation
    Alexander Marson
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 445:931-5. 2007
    ..Foxp3 suppression of its targets appears to be crucial for the normal function of T(reg) cells, because overactive variants of some target genes are known to be associated with autoimmune disease...
  82. doi request reprint DNA methylation controls Foxp3 gene expression
    Julia K Polansky
    Experimentelle Rheumatologie Experimentelle Immunregulation, Charite Universitaetsmedizin Berlin, Berlin, Germany
    Eur J Immunol 38:1654-63. 2008
    ..Together, our data suggest that TSDR is an important methylation-sensitive element regulating Foxp3 expression and demonstrate that epigenetic imprinting in this region is critical for establishment of a stable Treg lineage...
  83. ncbi request reprint Down-regulation of diabetogenic CD4+ T cells by a soluble dimeric peptide-MHC class II chimera
    Sofia Casares
    Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Nat Immunol 3:383-91. 2002
    ..Soluble dimeric pMHC class II may be useful in the development of immunospecific therapies for type 1 diabetes...
  84. pmc The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival
    Malay Mandal
    Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
    J Exp Med 201:603-14. 2005
    ..Finally, we suggest that pre-TCR-induced A1 overexpression can contribute to T cell leukemia in both mice and humans...
  85. ncbi request reprint Antigen-specific FoxP3-transduced T-cells can control established type 1 diabetes
    Elmar Jaeckel
    Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl Neuberg Str 1, 30625 Hannover, Germany
    Diabetes 54:306-10. 2005
    ..Our results complement recent results on in vitro-amplified antigen-specific T-cells in ameliorating type 1 diabetes and suggest that FoxP3 transduction of expanded T-cells might achieve the same goal...
  86. ncbi request reprint Commitment and developmental potential of extrathymic and intrathymic T cell precursors: plenty to choose from
    Avinash Bhandoola
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Immunity 26:678-89. 2007
    ..Such an understanding may also help ameliorate immunological defects in aging. This review covers the differentiation steps between HSCs and committed T cell progenitors within the thymus...
  87. ncbi request reprint Notch in lymphopoiesis and T cell polarization
    Harald von Boehmer
    Nat Immunol 6:641-2. 2005
  88. pmc Lymphocyte development: overview
    Klaus Rajewsky
    Curr Opin Immunol 20:127-30. 2008
  89. pmc Lineage diversion of T cell receptor transgenic thymocytes revealed by lineage fate mapping
    Takeshi Egawa
    Molecular Pathogenesis Program, The Helen L and Martin S Kimmel Center for Biology and Medicine, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York, USA
    PLoS ONE 3:e1512. 2008
    ....
  90. pmc Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias
    Keiko Miyoshi
    Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 99:219-24. 2002
    ..These data demonstrate that the activation of beta-catenin signaling induces a program that results in loss of mammary epithelial cell differentiation and induction of epidermal structures...

Research Grants25

  1. pTa-controlled reporter to identify lymphoid precursor
    Harald von Boehmer; Fiscal Year: 2003
    ..We will further characterize developmental stages with regard to expression and essential role of transcription factors involved in lineage commitment. ..
  2. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2007
    ..Gene expression analysis as a function of time after inducible ?? and pre-TCR expression and 3.) Analysis of development after knockdown of lineage-specific gene expression by RNAi. ..
  3. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2006
    ..Gene expression analysis as a function of time after inducible ?? and pre-TCR expression and 3.) Analysis of development after knockdown of lineage-specific gene expression by RNAi. ..
  4. MOLECULAR AND CELLULAR ANALYSIS OF PRE-TCR FUNCTION
    Harald von Boehmer; Fiscal Year: 2002
    ..The proposed experiments will elucidate the molecular mechanisms that mediate the function of the pre-TCR. ..
  5. MOLECULAR AND CELLULAR ANALYSIS OF PRE-TCR FUNCTION
    Harald von Boehmer; Fiscal Year: 2003
    ..The proposed experiments will elucidate the molecular mechanisms that mediate the function of the pre-TCR. ..
  6. Generation of antigen-specific regulation T cells
    Harald von Boehmer; Fiscal Year: 2007
    ..Ultimately, based on the observations in our transgenic systems, we will test lifferent protocols to experimentally induce Treg cells in vivo. ..
  7. pTa-controlled reporter to identify lymphoid precursor
    Harald von Boehmer; Fiscal Year: 2007
    ..We will further characterize developmental stages with regard to expression and essential role of transcription factors involved in lineage commitment. ..
  8. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2009
    ..Gene expression analysis as a function of time after inducible ySand pre-TCR expression and 3.) Analysis of development after knockdown of lineage-specific gene expression by RNAi. ..
  9. Extrathymic T cell precursors: commitment and efficacy
    Harald von Boehmer; Fiscal Year: 2009
    ..Identification of the extrathymic T cell precursors will help in the faster regeneration of the immune system after treatment of malignancy by x- irradiation and/or cytotoxic drugs that result in T cell depletion. ..
  10. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2010
    ..Gene expression analysis as a function of time after inducible ySand pre-TCR expression and 3.) Analysis of development after knockdown of lineage-specific gene expression by RNAi. ..
  11. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2000
    ..abstract_text> ..
  12. pTa-controlled reporter to identify lymphoid precursor
    Harald von Boehmer; Fiscal Year: 2006
    ..We will further characterize developmental stages with regard to expression and essential role of transcription factors involved in lineage commitment. ..
  13. MOLECULAR AND CELLULAR ANALYSIS OF PRE-TCR FUNCTION
    Harald von Boehmer; Fiscal Year: 2001
    ..The proposed experiments will elucidate the molecular mechanisms that mediate the function of the pre-TCR. ..
  14. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2001
    ..abstract_text> ..
  15. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2002
    ..abstract_text> ..
  16. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2003
    ..abstract_text> ..
  17. MOLECULAR AND CELLULAR ANALYSIS OF PRE-TCR FUNCTION
    Harald von Boehmer; Fiscal Year: 2004
    ..The proposed experiments will elucidate the molecular mechanisms that mediate the function of the pre-TCR. ..
  18. ROLE OF THE PRE-T CELL RECEPTOR IN LINEAGE COMMITMENT
    Harald von Boehmer; Fiscal Year: 2004
    ..abstract_text> ..
  19. MOLECULAR AND CELLULAR ANALYSIS OF PRE-TCR FUNCTION
    Harald von Boehmer; Fiscal Year: 2005
    ..The proposed experiments will elucidate the molecular mechanisms that mediate the function of the pre-TCR. ..
  20. Extrathymic T cell precursors: commitment and efficacy
    Harald von Boehmer; Fiscal Year: 2010
    ..Identification of the extrathymic T cell precursors will help in the faster regeneration of the immune system after treatment of malignancy by x- irradiation and/or cytotoxic drugs that result in T cell depletion. ..