title: Specific signaling pathways triggered by IL-2 in human V gamma 9V delta 2 T cells: an amalgamation of NK and alpha beta T cell signaling.
abstract: The global immune response can be simplified into two components: the innate and the acquired systems. The innate immune response comprises primarily macrophages and NK cells, while B and T cells orchestrate the acquired response. Human Vgamma9Vdelta2 T cells represent a minor T cell subpopulation in blood (1-5%) that is activated via the TCR by small nonpeptidic molecules. Their percentage dramatically increases during the early phase of infection by intracellular pathogens, and they display many characteristics of NK cells, which places them at a unique position within the immune system. Our aim was to explore the behavior of these cells when they are activated by a receptor that is common to NK and alphabeta T cells, and to determine signaling pathways and biological responses induced in these cells through this receptor. Thus, we investigated whether Vgamma9Vdelta2 T cells behave as NK cells or as alphabeta T cells. We demonstrated that IL-2 activates not only STAT3, STAT5, the phosphatidylinositol 3-kinase pathway, and extracellular signal-regulated kinase-2 pathway, but also STAT4 as in NK cells, and the p38 mitogen-activated protein kinase pathway as in alphabeta T cells. Moreover, IL-2 induces the production of IFN-gamma in Vgamma9Vdelta2 T cells as observed in NK cells. Due to their double profiles, Vgamma9Vdelta2 T cells are at the interface of the innate and the acquired immune response and may therefore not only modulate the activity of innate cells, but also influence Th1/Th2 differentiation.
authors: Institut National de la Santé et de la Recherche Médicale Unité 431, Université Montpellier 2, Montpellier, France. vlafont@crit.univ-montp2.fr
authors: Virginie
authors: V
authors: Lafont
authors: Séverine
authors: S
authors: Loisel
authors: Janny
authors: J
authors: Liautard
authors: Sherri
authors: S
authors: Dudal
authors: Magali
authors: M
authors: Sablé-Teychené
authors: Jean-Pierre
authors: JP
authors: Liautard
authors: Jean
authors: J
authors: Favero
mesh_terms: D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000502:physiology*; D053614:Janus Kinase 2; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D007376:Interleukin-2; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human