CD8+ T cell evasion mandates CD4+ T cell control of chronic gamma-herpesvirus infection

• Published in: PLoS pathogens 2017-04, Vol.13 (4), p.e1006311-e1006311
• Main Authors: Tan, Cindy S E, Lawler, Clara, Stevenson, Philip G
• Format: Article
• Language: English
• Subjects: Animals; Antigen presentation; Biology and Life Sciences; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Colleges & universities; Dendritic cells; Disease control; Disease Models, Animal; Disruption; Epitopes; Gene expression; Herpesviridae Infections - immunology; Herpesviridae Infections - virology; Histocompatibility Antigens Class I - immunology; Immunology; Infections; Lungs; Lymphocytes; Lymphocytes T; Lymphoma; Macrophages; Medicine and Health Sciences; Mice; Mice, Knockout; Research and Analysis Methods; Rhadinovirus - isolation & purification; Rodents
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006311

Gamma-herpesvirus infections are regulated by both CD4+ and CD8+ T cells. However clinical disease occurs mainly in CD4+ T cell-deficient hosts. In CD4+ T cell-deficient mice, CD8+ T cells control acute but not chronic lung infection by Murid Herpesvirus-4 (MuHV-4). We show that acute and chronic lung infections differ in distribution: most acute infection was epithelial, whereas most chronic infection was in myeloid cells. CD8+ T cells controlled epithelial infection, but CD4+ T cells and IFNγ were required to control myeloid cell infection. Disrupting the MuHV-4 K3, which degrades MHC class I heavy chains, increased viral epitope presentation by infected lung alveolar macrophages and allowed CD8+ T cells to prevent disease. Thus, viral CD8+ T cell evasion led to niche-specific immune control, and an essential role for CD4+ T cells in limiting chronic infection.