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

被引:69
作者
Walton, Senta M. [1 ]
Mandaric, Sanja [1 ]
Torti, Nicole [1 ]
Zimmermann, Albert [2 ]
Hengel, Hartmut [2 ]
Oxenius, Annette [1 ]
机构
[1] ETH, Inst Microbiol, CH-8092 Zurich, Switzerland
[2] Univ Dusseldorf, Inst Virol, Dusseldorf, Germany
基金
瑞士国家科学基金会;
关键词
TUMOR-NECROSIS-FACTOR; MHC CLASS-I; LONG-TERM DEPLETION; MURINE CYTOMEGALOVIRUS; NATURAL-KILLER; DENDRITIC CELLS; MOUSE CYTOMEGALOVIRUS; ANTIGEN PRESENTATION; INTERFERON-GAMMA; LYMPHOCYTES-T;
D O I
10.1371/journal.ppat.1002214
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
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 IFN gamma 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 IFN gamma, 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 IFN gamma secretion interfering with viral replication in cells of non-hematopoietic origin.
引用
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页数:14
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