Absence of Cross-Presenting Cells in the Salivary Gland and Viral Immune Evasion Confine Cytomegalovirus Immune Control to Effector CD4 T Cells

PLoS Pathogens

Hartmut Hengel¹  Albert Zimmermann¹  Senta M. Walton²  Annette Oxenius²  Sanja Mandaric²  Nicole Torti² 

[1] Institute for Virology, Heinrich-Heine-University Düsseldorf , Düsseldorf, Germany;Institute of Microbiology, ETH Zürich, Zürich, Switzerland

关键词: T helper cells;    Cytotoxic T cells;    T cells;    Major histocompatibility complex;    Antigen-presenting cells;    Viral replication;    NK cells;    MHC class I genes;   

DOI  :  10.1371/journal.ppat.1002214

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Horizontal transmission of cytomegaloviruses (CMV) occurs via prolonged excretion from mucosal surfaces. We used murine CMV (MCMV) infection to investigate the mechanisms of immune control in secretory organs. CD4 T cells were crucial to cease MCMV replication in the salivary gland (SG) via direct secretion of IFNγ that initiated antiviral signaling on non-hematopoietic cells. In contrast, CD4 T cell helper functions for CD8 T cells or B cells were dispensable. Despite SG-resident MCMV-specific CD8 T cells being able to produce IFNγ, the absence of MHC class I molecules on infected acinar glandular epithelial cells due to viral immune evasion, and the paucity of cross-presenting antigen presenting cells (APCs) prevented their local activation. Thus, local activation of MCMV-specific T cells is confined to the CD4 subset due to exclusive presentation of MCMV-derived antigens by MHC class II molecules on bystander APCs, resulting in IFNγ secretion interfering with viral replication in cells of non-hematopoietic origin.

【 授权许可】

CC BY