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PMID: 19542444 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The initial phase of an immune response functions to activate regulatory T cells.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 183 ·No. 1 ·2009-07-01 ·Pages 332-9

O'Gorman WE, Dooms H, Thorne SH, Kuswanto WF, Simonds EF, Krutzik PO, Nolan GP, Abbas AK

Abstract

An early reaction of CD4(+) T lymphocytes to Ag is the production of cytokines, notably IL-2. To detect cytokine-dependent responses, naive Ag-specific T cells were stimulated in vivo and the presence of phosphorylated STAT5 molecules was used to identify the cell populations responding to IL-2. Within hours of T cell priming, IL-2-dependent STAT5 phosphorylation occurred primarily in Foxp3(+) regulatory T cells. In contrast, the Ag-specific T cells received STAT5 signals only after repeated Ag exposure or memory differentiation. Regulatory T cells receiving IL-2 signals proliferated and developed enhanced suppressive activity. These results indicate that one of the earliest events in a T cell response is the activation of endogenous regulatory cells, potentially to prevent autoimmunity.

MeSH Terms
Animals Cell Proliferation Interleukin-2/biosynthesis,physiology Lymphocyte Activation/genetics,immunology Mice Mice, Inbred BALB C Mice, Knockout Mice, Transgenic Phosphorylation Resting Phase, Cell Cycle/genetics,immunology STAT5 Transcription Factor/metabolism Signal Transduction/genetics,immunology T-Lymphocyte Subsets/immunology,metabolism,virology T-Lymphocytes, Regulatory/immunology,metabolism,virology Time Factors Vaccinia virus/immunology
Chemicals
Interleukin-2 STAT5 Transcription Factor
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
O'Gorman William E
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305, USA.
Dooms Hans
Thorne Steve H
Kuswanto Wilson F
Simonds Erin F
Krutzik Peter O
Nolan Garry P
Abbas Abul K
References (42)
42 references, click to expand
  1. Intracellular phospho-protein staining techniques for flow cytometry: monitoring single cell signaling events.
    Cytometry A. 2003 Oct;55(2):61-70 PMID: 14505311
  2. Regulation of immunity by self-reactive T cells.
    Nature. 2005 Jun 2;435(7042):598-604 PMID: 15931212
  3. High-content single-cell drug screening with phosphospecific flow cytometry.
    Nat Chem Biol. 2008 Feb;4(2):132-42 PMID: 18157122
  4. Indexation as a novel mechanism of lymphocyte homeostasis: the number of CD4+CD25+ regulatory T cells is indexed to the number of IL-2-producing cells.
    J Immunol. 2006 Jul 1;177(1):192-200 PMID: 16785514
  5. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization.
    J Exp Med. 2005 Mar 7;201(5):723-35 PMID: 15753206
  6. Regulatory T cells: key controllers of immunologic self-tolerance.
    Cell. 2000 May 26;101(5):455-8 PMID: 10850488
  7. A natural immunological adjuvant enhances T cell clonal expansion through a CD28-dependent, interleukin (IL)-2-independent mechanism.
    J Exp Med. 1998 Jan 19;187(2):225-36 PMID: 9432980
  8. Suppressor of cytokine signaling 3 regulates proliferation and activation of T-helper cells.
    J Biol Chem. 2003 Aug 8;278(32):29752-9 PMID: 12783879
  9. Regulatory T cells and infection: a dangerous necessity.
    Nat Rev Immunol. 2007 Nov;7(11):875-88 PMID: 17948021
  10. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells.
    Nat Immunol. 2007 Dec;8(12):1353-62 PMID: 17982458
  11. CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses.
    J Exp Med. 2003 Sep 15;198(6):889-901 PMID: 12975455
  12. Regulatory T cell lineage specification by the forkhead transcription factor foxp3.
    Immunity. 2005 Mar;22(3):329-41 PMID: 15780990
  13. SOCS proteins, cytokine signalling and immune regulation.
    Nat Rev Immunol. 2007 Jun;7(6):454-65 PMID: 17525754
  14. Characterization of the murine immunological signaling network with phosphospecific flow cytometry.
    J Immunol. 2005 Aug 15;175(4):2366-73 PMID: 16081807
  15. Deficient SOCS3 expression in CD4+CD25+FoxP3+ regulatory T cells and SOCS3-mediated suppression of Treg function.
    Eur J Immunol. 2007 Aug;37(8):2082-9 PMID: 17621372
  16. Single cell profiling of potentiated phospho-protein networks in cancer cells.
    Cell. 2004 Jul 23;118(2):217-28 PMID: 15260991
  17. T cell fitness determined by signal strength.
    Nat Immunol. 2003 Apr;4(4):355-60 PMID: 12640450
  18. Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other gamma c-dependent cytokines in peripheral T cells.
    J Biol Chem. 2003 Jun 20;278(25):22755-61 PMID: 12665516
  19. Coordination of early protective immunity to viral infection by regulatory T cells.
    Science. 2008 May 30;320(5880):1220-4 PMID: 18436744
  20. Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells.
    Nature. 2006 Jun 15;441(7095):890-3 PMID: 16778891
  21. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells.
    Science. 2003 Feb 14;299(5609):1033-6 PMID: 12532024
  22. The role of Stat5a and Stat5b in signaling by IL-2 family cytokines.
    Oncogene. 2000 May 15;19(21):2566-76 PMID: 10851055
  23. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein.
    Immunity. 2009 Jan 16;30(1):80-91 PMID: 19144316
  24. Real-time manipulation of T cell-dendritic cell interactions in vivo reveals the importance of prolonged contacts for CD4+ T cell activation.
    Immunity. 2007 Oct;27(4):625-34 PMID: 17950004
  25. Continuous activation of autoreactive CD4+ CD25+ regulatory T cells in the steady state.
    J Exp Med. 2003 Sep 1;198(5):737-46 PMID: 12939344
  26. Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7R alpha-expressing cells.
    J Exp Med. 2007 Mar 19;204(3):547-57 PMID: 17312008
  27. A low interleukin-2 receptor signaling threshold supports the development and homeostasis of T regulatory cells.
    Immunity. 2009 Feb 20;30(2):204-17 PMID: 19185518
  28. SOCS-3 is tyrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation.
    Mol Cell Biol. 1999 Jul;19(7):4980-8 PMID: 10373548
  29. Interleukin-2: inception, impact, and implications.
    Science. 1988 May 27;240(4856):1169-76 PMID: 3131876
  30. IL-2 secretion by CD4+ T cells in vivo is rapid, transient, and influenced by TCR-specific competition.
    J Immunol. 2004 May 15;172(10):6136-43 PMID: 15128800
  31. Selective stimulation of T cell subsets with antibody-cytokine immune complexes.
    Science. 2006 Mar 31;311(5769):1924-7 PMID: 16484453
  32. Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen.
    J Exp Med. 2005 Nov 21;202(10):1375-86 PMID: 16287710
  33. Mechanisms of suppression by suppressor T cells.
    Nat Immunol. 2005 Apr;6(4):338-44 PMID: 15785759
  34. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity.
    Nature. 2002 Dec 5;420(6915):502-7 PMID: 12466842
  35. Cutting edge: Paracrine, but not autocrine, IL-2 signaling is sustained during early antiviral CD4 T cell response.
    J Immunol. 2006 Oct 1;177(7):4257-61 PMID: 16982857
  36. Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors.
    Immunity. 2004 Aug;21(2):267-77 PMID: 15308106
  37. Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1.
    Nat Immunol. 2003 Nov;4(11):1083-92 PMID: 14528303
  38. Natural versus adaptive regulatory T cells.
    Nat Rev Immunol. 2003 Mar;3(3):253-7 PMID: 12658273
  39. Single-cell phospho-protein analysis by flow cytometry.
    Curr Protoc Immunol. 2007 Aug;Chapter 8:Unit 8.17 PMID: 18432997
  40. IL-2 induces a competitive survival advantage in T lymphocytes.
    J Immunol. 2004 May 15;172(10):5973-9 PMID: 15128779
  41. A function for interleukin 2 in Foxp3-expressing regulatory T cells.
    Nat Immunol. 2005 Nov;6(11):1142-51 PMID: 16227984
  42. Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells.
    Immunity. 2008 Nov 14;29(5):758-70 PMID: 19006694
Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
Published
2009-07-01
Pages
332-9
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC2753472
Subset
IM
Grants
NIAID NIH HHS · P01 AI035297 · United States
NIAID NIH HHS · P01 AI036535 · United States
NHLBI NIH HHS · N01-HV-28183 · United States
NIAID NIH HHS · R01 AI065824 · United States
NIAID NIH HHS · R01 AI073656 · United States
NIAID NIH HHS · P01 AI35297 · United States
NIAID NIH HHS · R01 AI073656-01A1 · United States
NHLBI NIH HHS · N01HV28183 · United States
NIAID NIH HHS · P01 AI035297-150001 · United States
NHLBI NIH HHS · N01 HV028183 · United States
NIAID NIH HHS · P01 AI036535-080006 · United States
NIAID NIH HHS · P01 AI36535 · United States
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