期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 9, 页码 2290-2304出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201142275
关键词
Antigen amount; CD8+T cell; Chronic viral infection; Dysfunction; Immunopathology
类别
资金
- ETH Zurich
- Swiss National Science Foundation [310030-129751]
- Swiss National Science Foundation (SNF) [310030_129751] Funding Source: Swiss National Science Foundation (SNF)
Chronic viral infections lead to CD8+ T-cell exhaustion, characterized by impaired cytokine secretion and loss of proliferative capacity. While viral load and T-cell dysfunction correlate, it is currently unclear whether the quality of a cell type presenting antigen determines the degree of T-cell exhaustion or if the overall amount of antigen recognized by T cells promotes exhaustion. We found that chronic lymphocytic chorio-meningitis virus infection led to decreased CD8+ T-cell exhaustion in DC-MHC class I (MHCI) mice, in which CD8+ T cells can only recognize antigen on DCs. However, this increase in CD8+ T-cell function came at the expense of fatal immunopathology. Additional antigen recognition on nonhematopoietic cells in DC-MHCI mice promoted T-cell exhaustion and avoidance of immunopathology. Likewise, increased numbers of antigen-expressing hematopoietic cells, as well as a selective elevation of the number of DCs as the only cell type presenting antigen in DC-MHCI mice, resulted in compromised T-cell function. These results favor a scenario in which the overall amount of antigen exposure, rather than the type of cell engaging with virus-specific CD8+ T cells, is responsible for their functional exhaustion. Furthermore, exhaustion of virus-specific CD8+ T cells leads to avoidance of life-threatening immunopathology.
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