T helper 1 effector memory CD4+ T cells protect the skin from poxvirus infection
Jake C. Harbour,
Mahmoud Abdelbary,
John B. Schell,
Samantha P. Fancher,
Jack J. McLean,
Taylen J. Nappi,
Susan Liu,
Timothy J. Nice,
Zheng Xia,
Klaus Früh,
Jeffrey C. Nolz
Affiliations
Jake C. Harbour
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
Mahmoud Abdelbary
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
John B. Schell
Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA
Samantha P. Fancher
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
Jack J. McLean
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
Taylen J. Nappi
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
Susan Liu
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA
Timothy J. Nice
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
Zheng Xia
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA
Klaus Früh
Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA
Jeffrey C. Nolz
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR, USA; Department of Dermatology, Oregon Health & Science University, Portland, OR, USA; Corresponding author
Summary: 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 γ (IFNγ) 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 IFNγ-dependent manner, and require IFNγ receptor (IFNγR) 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 keratinocytes are the key targets of IFNγ necessary for preventing poxvirus infection of the epidermis.
