Recruitment,Phenotype,and Functional Mechanism Of Airway T Cells During Influenza Virus Infection

Background:Influenza virus infection can cause worldwide morbidity and mortality,especially for children and the elderly.Since influenza virus infection and replication take place in the respiratory epithelial cells,airway T cells are considered pivotal for eliminating virus.However,there is no data to systematically study the phenotypic characteristics,recruitment,and functional mechanisms of airway CD4+T and CD8+T cells at different stages of infection,which may help to develop influenza vaccines or adjuvants based on induced airway T cells.Objective:To systematically investigate the recruitment,phenotype and functional mechanism of airway T cells by using influenza virus infection mouse model,and to provide reference for the development of influenza virus vaccines or adjuvants based on mucosal T cells.METHODS:Based on influenza virus-infected mouse models,flow cytometry analysis and sorting were used to detect the dynamic changes of T cell in the respiratory tract;Neutralizing antibodies were used to block lung IFN-?,CXCR3,ICAM-1 and CD62L,respectively,to study the recruitment mechanism of airway T cells;Flow cytometry sorting and quantitative PCR were used to detect the phenotypes of airway T cells?transcriptional features and surface markers?;influenza virus-induced airway T cell responses were detected by ELISPOT,ICS,and quantitative PCR;neutralizing antibodies were blocked recruitment of airway T cells was studied for its protective effect and mechanism in primary infection;the protective effect and mechanism of reinfection were studied by deleting airway T cells.Results:After the initial influenza virus infection,airway T cells began to recruit in the respiratory tract on the 2-4^th day,reached a peak on 7 days,reached a stable state on28 days,and persisted for 160days.We found that IFN-?and its induced chemokines?CXCL9,CXCL10,CXCL11?and adhesion molecules?ICAM-1?,CD62L,together mediate recruitment of T cells in the respiratory tract.Airway T cells exhibited effector-like and tissue-resident phenotypes.Resting airway T cells were highly inhibited,but cytotoxic molecules?granzyme B?and regulatory factors?IL-10?were continuously expressed.T cells recruited to the respiratory tract play a protective role by proliferating,secreting antiviral cytokines and cytotoxic molecules.Blocking the recruitment of airway T cells reduces the protection for influenza virus primary infection.Reactivated airway T cells are rapidly activated to produce a strong antiviral factor?IFN-??,which induced the production of chemokines to recruit various immune cells,and establish an antivirual state.In addition,the deletion of airway T cells reduces protection for reinfection of influenza virus.Conclusion:We revealed that the phenotypic characteristics and recruitment mechanism of airway T cells during influenza virus infection.It was found that IFN-?-mediated recruitment of airway T cells plays an critical role in host response to influenza virus infection.