Suppression of Cytotoxic T Cell Functions and Decreased Levels of Tissue Resident Memory T cell During H5N1 infection

Abstract

25Seasonal influenza virus infections cause mild illness in healthy adults, as timely viral 26 clearance is mediated by the functions of cytotoxic T cells. However, avian H5N1 influenza 27 virus infections can result in prolonged and fatal illness across all age groups, which has been 28 attributed to the overt and uncontrolled activation of host immune responses. Here we 29 investigate how excessive innate immune responses to H5N1 impair subsequent adaptive T 30 cell responses in the lungs. Using recombinant H1N1 and H5N1 strains sharing 6 internal 31 genes, we demonstrate that H5N1 (2:6) infection in mice causes higher stimulation and 32 increased migration of lung dendritic cells to the draining lymph nodes, resulting in higher 33 numbers of virus specific T cells in the lungs. Despite robust T cell responses in the lungs, 34 H5N1 (2:6) infected mice showed inefficient and delayed viral clearance as compared to H1N1 35 infected mice. In addition, we observed higher levels of inhibitory signals including increased 36 PD1 and IL-10 expression by cytotoxic T cells in H5N1 (2:6) infected mice, suggesting that 37 delayed viral clearance of H5N1 (2:6) was due to suppression of T cell functions in vivo. 38

Reliability of Self-Sampling for Accurate Assessment of Respiratory Virus Viral and Immunologic Kinetics

“…Another major unmet medical need is the ability to frequently measure the local mucosal immune response during the course of infection. It is increasingly recognized that tissue resident T-cells and antigen presenting cells are phenotypically and functionally distinct from circulating immune cells, especially in the setting of respiratory viral infections [18][19][20] . Therefore, measuring immune cells in blood can fundamentally misclassify the agents responsible for viral elimination at the local level.…”

Reliability of self-sampling for accurate assessment of respiratory virus viral and immunologic kinetics

“…Another major unmet medical need is the ability to frequently measure the local mucosal immune response during the course of infection. It is increasingly recognized that tissue resident T-cells and antigen presenting cells are phenotypically and functionally distinct from circulating immune cells, especially in the setting of respiratory viral infections 18-20 . Therefore, measuring immune cells in blood can fundamentally misclassify the agents responsible for viral elimination at the local level.…”