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

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. © 2017 tan et al.