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Specific Signaling Pathways Triggered by IL-2 in Human V9V2 T Cells: An Amalgamation of NK and T Cell Signaling ¹

Institut National de la Santé et de la Recherche Médicale Unité 431, Université Montpellier 2, Montpellier, France

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 V9V2 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 T cells, and to determine signaling pathways and biological responses induced in these cells through this receptor. Thus, we investigated whether V9V2 T cells behave as NK cells or as 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 T cells. Moreover, IL-2 induces the production of IFN- in V9V2 T cells as observed in NK cells. Due to their double profiles, V9V2 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.

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