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De Giovanni, Marco; Cutillo, Valeria; Giladi, Amir; Sala, Eleonora; Maganuco, Carmela G; Medaglia, Chiara; Di Lucia, Pietro; Bono, Elisa; Cristofani, Claudia; Consolo, Eleonora; Giustini, Leonardo; Fiore, Alessandra; Eickhoff, Sarah; Kastenmüller, Wolfgang; Amit, Ido; Kuka, Mirela; Iannacone, Matteo
Nature immunology, 03/2020, Letnik: 21, Številka: 3Journal Article
Differentiation of CD4 T cells into either follicular helper T (T ) or type 1 helper T (T 1) cells influences the balance between humoral and cellular adaptive immunity, but the mechanisms whereby pathogens elicit distinct effector cells are incompletely understood. Here we analyzed the spatiotemporal dynamics of CD4 T cells during infection with recombinant vesicular stomatitis virus (VSV), which induces early, potent neutralizing antibodies, or recombinant lymphocytic choriomeningitis virus (LCMV), which induces a vigorous cellular response but inefficient neutralizing antibodies, expressing the same T cell epitope. Early exposure of dendritic cells to type I interferon (IFN), which occurred during infection with VSV, induced production of the cytokine IL-6 and drove T cell polarization, whereas late exposure to type I IFN, which occurred during infection with LCMV, did not induce IL-6 and allowed differentiation into T 1 cells. Thus, tight spatiotemporal regulation of type I IFN shapes antiviral CD4 T cell differentiation and might instruct vaccine design strategies.
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