tetano
Editor, Senior Moderator
J Immunol
. 2022 Apr 13;ji2101021.
doi: 10.4049/jimmunol.2101021. Online ahead of print.
Pneumonia Severity and Phase Linked to Virus-Specific T Cell Responses with Distinct Immune Checkpoints during pH1N1 Infection
Hui Li[SUP] 1 [/SUP], Min Zhao[SUP] 2 3 [/SUP], Hangjie Zhang[SUP] 4 [/SUP], Chuansong Quan[SUP] 4 [/SUP], Dannie Zhang[SUP] 4 [/SUP], Yingmei Liu[SUP] 1 [/SUP], Meng Liu[SUP] 5 [/SUP], Chunxue Xue[SUP] 5 [/SUP], Shuguang Tan[SUP] 2 [/SUP], Yaxin Guo[SUP] 4 [/SUP], Yingze Zhao[SUP] 4 [/SUP], Guizhen Wu[SUP] 4 [/SUP], George F Gao[SUP] 6 3 4 [/SUP], Bin Cao[SUP] 7 5 8 [/SUP], William J Liu[SUP] 9 10 [/SUP]
Affiliations
Abstract
The detailed features and the longitudinal variation of influenza-specific T cell responses within naturally infected patients and the relationship with disease severity remain uncertain. In this study, we characterized the longitudinal influenza-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses, T cell activation, and migration-related cytokine/chemokine secretion in pH1N1-infected patients with or without viral pneumonia with human PBMCs. Both the influenza-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells presented higher responses in patients with severe infection than in mild ones, but with distinct longitudinal variations, phenotypes of memory markers, and immune checkpoints. At 7 ± 3 d after onset of illness, effector CD8[SUP]+[/SUP] T cells (CD45RA[SUP]+[/SUP]CCR7[SUP]-[/SUP]) with high expression of inhibitory immune receptor CD200R dominated the specific T cell responses. However, at 21 ± 3 d after onset of illness, effector memory CD4[SUP]+[/SUP] T cells (CD45RA[SUP]-[/SUP]CCR7[SUP]-[/SUP]) with high expression of PD1, CTLA4, and LAG3 were higher among the patients with severe disease. The specific T cell magnitude, T cell activation, and migration-related cytokines/chemokines possessed a strong connection with disease severity. Our findings illuminate the distinct characteristics of immune system activation during dynamic disease phases and its correlation with lung injury of pH1N1 patients.
. 2022 Apr 13;ji2101021.
doi: 10.4049/jimmunol.2101021. Online ahead of print.
Pneumonia Severity and Phase Linked to Virus-Specific T Cell Responses with Distinct Immune Checkpoints during pH1N1 Infection
Hui Li[SUP] 1 [/SUP], Min Zhao[SUP] 2 3 [/SUP], Hangjie Zhang[SUP] 4 [/SUP], Chuansong Quan[SUP] 4 [/SUP], Dannie Zhang[SUP] 4 [/SUP], Yingmei Liu[SUP] 1 [/SUP], Meng Liu[SUP] 5 [/SUP], Chunxue Xue[SUP] 5 [/SUP], Shuguang Tan[SUP] 2 [/SUP], Yaxin Guo[SUP] 4 [/SUP], Yingze Zhao[SUP] 4 [/SUP], Guizhen Wu[SUP] 4 [/SUP], George F Gao[SUP] 6 3 4 [/SUP], Bin Cao[SUP] 7 5 8 [/SUP], William J Liu[SUP] 9 10 [/SUP]
Affiliations
- PMID: 35418471
- DOI: 10.4049/jimmunol.2101021
Abstract
The detailed features and the longitudinal variation of influenza-specific T cell responses within naturally infected patients and the relationship with disease severity remain uncertain. In this study, we characterized the longitudinal influenza-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses, T cell activation, and migration-related cytokine/chemokine secretion in pH1N1-infected patients with or without viral pneumonia with human PBMCs. Both the influenza-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells presented higher responses in patients with severe infection than in mild ones, but with distinct longitudinal variations, phenotypes of memory markers, and immune checkpoints. At 7 ± 3 d after onset of illness, effector CD8[SUP]+[/SUP] T cells (CD45RA[SUP]+[/SUP]CCR7[SUP]-[/SUP]) with high expression of inhibitory immune receptor CD200R dominated the specific T cell responses. However, at 21 ± 3 d after onset of illness, effector memory CD4[SUP]+[/SUP] T cells (CD45RA[SUP]-[/SUP]CCR7[SUP]-[/SUP]) with high expression of PD1, CTLA4, and LAG3 were higher among the patients with severe disease. The specific T cell magnitude, T cell activation, and migration-related cytokines/chemokines possessed a strong connection with disease severity. Our findings illuminate the distinct characteristics of immune system activation during dynamic disease phases and its correlation with lung injury of pH1N1 patients.