Journal
CELL REPORTS
Volume 42, Issue 5, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2023.112407
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This study found that Th1 memory CD4+ T cells are crucial for protecting against poxvirus skin infections, while CD8+ T cells are not necessary. Th1 effector memory CD4+ T cells rapidly infiltrate the poxvirus-infected skin microenvironment and produce interferon γ to promote anti-viral immunity. Keratinocytes are the key targets of IFNγ necessary for preventing poxvirus infection of the epidermis.
Poxvirus infections of the skin are a recent emerging public health concern, yet the mechanisms that mediate protective immunity against these viral infections remain largely unknown. Here, we show that T helper 1 (Th1) memory CD4+T cells are necessary and sufficient to provide complete and broad protection against poxvirus skin infections, whereas memory CD8+ T cells are dispensable. Core 2 O-glycan-synthesizing Th1 effector memory CD4+ T cells rapidly infiltrate the poxvirus-infected skin microenvironment and produce interferon y (IFNy) in an antigen-dependent manner, causing global changes in gene expression to promote anti-viral immunity. Keratinocytes express IFN-stimulated genes, upregulate both major histocompatibility complex (MHC) class I and MHC class II antigen presentation in an IFNy-dependent manner, and require IFNy receptor (IFNyR) signaling and MHC class II expression for memory CD4+ T cells to protect the skin from poxvirus infection. Thus, Th1 effector memory CD4+ T cells exhibit potent anti-viral activity within the skin, and kera-tinocytes are the key targets of IFNy necessary for preventing poxvirus infection of the epidermis.
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