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

PLoS Pathogens

Philip G. Stevenson¹  Cindy S. E. Tan¹  Clara Lawler¹ 

[1] School of Chemistry and Molecular Biosciences, University of Queensland and Royal Children’s Hospital, Brisbane, Australia

关键词: T cells;    Cytotoxic T cells;    Major histocompatibility complex;    Infectious disease control;    Bone marrow cells;    B cells;    Cell staining;    Viral replication;   

DOI  :  10.1371/journal.ppat.1006311

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY