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PMID: 16014561 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

T-bet is required for optimal proinflammatory CD4+ T-cell trafficking.

Blood ·Vol. 106 ·No. 10 ·2005-11-15 ·Pages 3432-9

Lord GM, Rao RM, Choe H, Sullivan BM, Lichtman AH, Luscinskas FW, Glimcher LH

Abstract

Inflammatory responses are controlled by T helper 1 (Th1) lymphocytes. An important function of this polarity is the ability of T cells to traffick appropriately in vivo. This differential trafficking is dependent upon the binding of P-selectin glycoprotein ligand-1 to P- and E-selectin on inflamed endothelium as well as the expression of specific chemokine receptors. Here we show that in the absence of T-box expressed in T cells (T-bet), selective migration of T cells in vivo is completely abrogated and that T-bet regulates the binding of CD4(+) T cells to P-selectin. T-bet is also required for the expression of the chemokine receptor CXCR3. Thus, T-bet controls Th1-cell migration to inflammatory sites, which has fundamental consequences for the control of immunologic disease.

MeSH Terms
Animals Cell Movement/genetics,immunology Cells, Cultured E-Selectin/immunology,metabolism Gene Expression Regulation/genetics,immunology Inflammation/genetics,immunology Membrane Glycoproteins/immunology,metabolism Mice Mice, Inbred BALB C Mice, Knockout P-Selectin/immunology,metabolism Protein Binding/immunology Receptors, Chemokine/genetics,immunology T-Box Domain Proteins Th1 Cells/immunology Transcription Factors/genetics,immunology,metabolism
Chemicals
E-Selectin Membrane Glycoproteins P-Selectin P-selectin ligand protein Receptors, Chemokine T-Box Domain Proteins T-box transcription factor TBX21 Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lord Graham M
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Rao Ravi M
Choe Hyeryun
Sullivan Brandon M
Lichtman Andrew H
Luscinskas F William
Glimcher Laurie H
References (50)
50 references, click to expand
  1. Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling.
    Cell. 2002 Sep 6;110(5):599-11 PMID: 12230977
  2. P-Selectin glycoprotein ligand 1 (PSGL-1) is a physiological ligand for E-selectin in mediating T helper 1 lymphocyte migration.
    J Exp Med. 2000 Dec 4;192(11):1669-76 PMID: 11104809
  3. Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis.
    Nat Med. 2002 Dec;8(12):1414-20 PMID: 12415259
  4. N-terminal residues in murine P-selectin glycoprotein ligand-1 required for binding to murine P-selectin.
    Blood. 2003 Jan 15;101(2):552-9 PMID: 12393631
  5. Molecular mechanisms regulating Th1 immune responses.
    Annu Rev Immunol. 2003;21:713-58 PMID: 12500979
  6. Heterogeneity of endothelial cells from different organ sites in T-cell subset recruitment.
    Am J Pathol. 2003 May;162(5):1591-601 PMID: 12707043
  7. Antibody-mediated blockade of the CXCR3 chemokine receptor results in diminished recruitment of T helper 1 cells into sites of inflammation.
    J Leukoc Biol. 2003 Jun;73(6):771-80 PMID: 12773510
  8. T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells.
    Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7749-54 PMID: 12802010
  9. The biology and enzymology of protein tyrosine O-sulfation.
    J Biol Chem. 2003 Jul 4;278(27):24243-6 PMID: 12730193
  10. Genetic reprogramming of primary human T cells reveals functional plasticity in Th cell differentiation.
    J Immunol. 2003 Oct 1;171(7):3542-9 PMID: 14500650
  11. A key pathogenic role for the STAT1/T-bet signaling pathway in T-cell-mediated liver inflammation.
    Hepatology. 2003 Dec;38(6):1573-80 PMID: 14647068
  12. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1.
    Nature. 2004 Jan 22;427(6972):355-60 PMID: 14737169
  13. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells.
    Annu Rev Immunol. 2004;22:891-928 PMID: 15032599
  14. T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells.
    Immunity. 2004 Apr;20(4):477-94 PMID: 15084276
  15. T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes.
    J Exp Med. 2004 Apr 19;199(8):1153-62 PMID: 15096540
  16. Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities.
    J Allergy Clin Immunol. 2004 May;113(5):987-94 PMID: 15131585
  17. T-box transcription-factor-deficient mice display increased joint pathology and failure of infection control during staphylococcal arthritis.
    Microbes Infect. 2004 May;6(6):529-35 PMID: 15158185
  18. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis.
    J Exp Med. 2004 Jul 5;200(1):79-87 PMID: 15238607
  19. CD4+CD25+ cells controlling a pathogenic CD4 response inhibit cytokine differentiation, CXCR-3 expression, and tissue invasion.
    J Immunol. 2004 Sep 1;173(5):2942-51 PMID: 15322152
  20. Improved version of a human CD2 minigene based vector for T cell-specific expression in transgenic mice.
    J Immunol Methods. 1995 Sep 11;185(1):133-40 PMID: 7665895
  21. Tyrosine sulfation of P-selectin glycoprotein ligand-1 is required for high affinity binding to P-selectin.
    J Biol Chem. 1995 Sep 29;270(39):22677-80 PMID: 7559387
  22. Functional diversity of helper T lymphocytes.
    Nature. 1996 Oct 31;383(6603):787-93 PMID: 8893001
  23. P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflammed tissues.
    Nature. 1997 Jan 2;385(6611):81-3 PMID: 8985251
  24. Role of PSGL-1 binding to selectins in leukocyte recruitment.
    J Clin Invest. 1997 Dec 1;100(11 Suppl):S97-103 PMID: 9413410
  25. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.
    J Exp Med. 1998 Jan 5;187(1):129-34 PMID: 9419219
  26. Chemokines and the arrest of lymphocytes rolling under flow conditions.
    Science. 1998 Jan 16;279(5349):381-4 PMID: 9430588
  27. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.
    J Exp Med. 1998 Mar 16;187(6):875-83 PMID: 9500790
  28. Identification of N-terminal residues on P-selectin glycoprotein ligand-1 required for binding to P-selectin.
    J Biol Chem. 1998 Mar 20;273(12):7078-87 PMID: 9507018
  29. Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry.
    Cell. 1999 Mar 5;96(5):667-76 PMID: 10089882
  30. Expression of functional selectin ligands on Th cells is differentially regulated by IL-12 and IL-4.
    J Immunol. 1999 Mar 15;162(6):3193-201 PMID: 10092770
  31. Migration and function of antigen-primed nonpolarized T lymphocytes in vivo.
    J Exp Med. 2001 Apr 16;193(8):987-93 PMID: 11304560
  32. Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines.
    Nat Immunol. 2001 Jun;2(6):515-22 PMID: 11376338
  33. IL-12, STAT4-dependent up-regulation of CD4(+) T cell core 2 beta-1,6-n-acetylglucosaminyltransferase, an enzyme essential for biosynthesis of P-selectin ligands.
    J Immunol. 2001 Oct 15;167(8):4476-84 PMID: 11591774
  34. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells.
    Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15137-42 PMID: 11752460
  35. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells.
    Science. 2002 Jan 11;295(5553):338-42 PMID: 11786644
  36. Molecular mechanisms involved in lymphocyte recruitment in inflamed brain microvessels: critical roles for P-selectin glycoprotein ligand-1 and heterotrimeric G(i)-linked receptors.
    J Immunol. 2002 Feb 15;168(4):1940-9 PMID: 11823530
  37. T-bet regulates IgG class switching and pathogenic autoantibody production.
    Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5545-50 PMID: 11960012
  38. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease.
    J Exp Med. 2002 May 6;195(9):1129-43 PMID: 11994418
  39. The role of P-selectin in experimental colitis as determined by antibody immunoblockade and genetically deficient mice.
    J Leukoc Biol. 2002 Jul;72(1):56-64 PMID: 12101263
  40. Induction of the chemokine receptor CXCR3 on TCR-stimulated T cells: dependence on the release from persistent TCR-triggering and requirement for IFN-gamma stimulation.
    Eur J Immunol. 2002 Jun;32(6):1792-801 PMID: 12115663
  41. Further checkpoints in Th1 development.
    Immunity. 2002 Jun;16(6):755-8 PMID: 12121657
  42. Acquisition of selectin binding and peripheral homing properties by CD4(+) and CD8(+) T cells.
    J Exp Med. 1999 Jun 7;189(11):1765-76 PMID: 10359580
  43. Expression of selectin ligands on murine effector and IL-10-producing CD4+ T cells from non-infected and infected tissues.
    Eur J Immunol. 2004 Nov;34(11):3070-81 PMID: 15384048
  44. Differential requirements for the O-linked branching enzyme core 2 beta1-6-N-glucosaminyltransferase in biosynthesis of ligands for E-selectin and P-selectin.
    Blood. 2001 Jun 15;97(12):3806-11 PMID: 11389020
  45. Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver.
    J Immunol. 1999 Dec 1;163(11):6236-43 PMID: 10570316
  46. Tyrosine replacement in P-selectin glycoprotein ligand-1 affects distinct kinetic and mechanical properties of bonds with P- and L-selectin.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13771-6 PMID: 10570148
  47. Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration.
    J Exp Med. 1999 Dec 20;190(12):1769-82 PMID: 10601352
  48. Th1/Th2 subsets: distinct differences in homing and chemokine receptor expression?
    Springer Semin Immunopathol. 1999;21(3):263-85 PMID: 10666773
  49. A novel transcription factor, T-bet, directs Th1 lineage commitment.
    Cell. 2000 Mar 17;100(6):655-69 PMID: 10761931
  50. Glycosylation in the control of selectin counter-receptor structure and function.
    Immunol Rev. 2002 Aug;186:19-36 PMID: 12234359
Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2005-04-1393
Published
2005-11-15
Epub
2005-00-12
Pages
3432-9
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895048
Subset
IM
Grants
Medical Research Council · G108/380 · United Kingdom
NIAID NIH HHS · AI48126 · United States
NHLBI NIH HHS · HL36028 · United States
NHLBI NIH HHS · HL53993 · United States
External Links
PubMed source DOI: 10.1182/blood-2005-04-1393 PMC Full Text View journal details
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