Acute viral respiratory infection rapidly induces a CD8+ T cell exhaustion-like phenotype

John J. Erickson, Pengcheng Lu, Sherry Wen, Andrew K. Hastings, Pavlo Gilchuk, Sebastian Joyce, Yu Shyr, John V. Williams

研究成果: Article同行評審

15 引文 斯高帕斯(Scopus)

摘要

Acute viral infections typically generate functional effector CD8+ T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors.

原文English
頁(從 - 到)4319-4330
頁數12
期刊Journal of Immunology
195
發行號9
DOIs
出版狀態Published - 2015 十一月

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

指紋 深入研究「Acute viral respiratory infection rapidly induces a CD8<sup>+</sup> T cell exhaustion-like phenotype」主題。共同形成了獨特的指紋。

引用此