Open AccessSpatiotemporal regulation of type I interferon expression determines the antiviral polarization of CD4+ T cells
Author(s) -
Marco De Giovanni,
Valeria Cutillo,
Amir Giladi,
Eleonora Sala,
Carmela G. Maganuco,
Chiara Medaglia,
Pietro Di Lucia,
Elisa Bono,
Claudia Cristofani,
Eleonora Consolo,
Leonardo Giustini,
Alessandra Fiore,
Sarah Eickhoff,
Wolfgang Kastenmüller,
Mirela Kuka,
Matteo Iannacone
Publication year - 2020
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-020-0596-6
Subject(s) - vesicular stomatitis virus , biology , lymphocytic choriomeningitis , interferon , immunology , virology , antibody , cytokine , interleukin 21 , effector , t cell , microbiology and biotechnology , virus , immune system , cd8
Differentiation of CD4 + T cells into either follicular helper T (T FH ) or type 1 helper T (T H 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 FH 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 H 1 cells. Thus, tight spatiotemporal regulation of type I IFN shapes antiviral CD4 + T cell differentiation and might instruct vaccine design strategies.