Pneumonia Severity and Phase Linked to Virus-Specific T Cell Responses with Distinct Immune Checkpoints during pH1N1 Infection

Author:

Li Hui1ORCID,Zhao Min23,Zhang Hangjie4,Quan Chuansong4,Zhang Dannie4,Liu Yingmei1,Liu Meng5,Xue Chunxue5,Tan Shuguang2,Guo Yaxin4ORCID,Zhao Yingze4,Wu Guizhen4,Gao George F.234ORCID,Cao Bin156,Liu William J.47ORCID

Affiliation:

1. *Department of Pulmonary and Critical Care Medicine, Laboratory of Clinical Microbiology and Infectious Diseases, China-Japan Friendship Hospital, Beijing, China;

2. †CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China;

3. ‡University of Chinese Academy of Sciences, Beijing, China;

4. §NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China;

5. ¶Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, China;

6. ‖Tsinghua University–Peking University Joint Center for Life Sciences, Beijing, China; and

7. #Research Unit of Adaptive Evolution and Control of Emerging Viruses, Chinese Academy of Medical Sciences, Beijing, China

Abstract

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+ and CD8+ 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+ and CD8+ 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+ T cells (CD45RA+CCR7−) 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+ T cells (CD45RA−CCR7−) 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.

Funder

National Science Fund for Distinguished Young Scholars

the Excellent Young Scientist Program of the National Natural Science Foundation of China

National Natural Science Foundation of China

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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