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.
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.
Lafont
Virginie
V
Institut National de la Santé et de la Recherche Médicale Unité 431, Université Montpellier 2, Montpellier, France. vlafont@crit.univ-montp2.fr
Loisel
Séverine
S
Liautard
Janny
J
Dudal
Sherri
S
Sablé-Teychené
Magali
M
Liautard
Jean-Pierre
JP
Favero
Jean
J
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
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