CD49a Identifies Polyfunctional Memory CD8 T cell Subsets that Persist in the Lungs after Influenza Infection
| Autor: | Emma C. Reilly, Mike Sportiello, Kris Lambert Emo, Andrea M. Amitrano, Rakshanda Jha, Ashwin B. R. Kumar, Nathan G. Laniewski, Hongmei Yang, Minsoo Kim, David J. Topham |
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| Rok vydání: | 2021 |
| Předmět: |
Cytotoxicity
Immunologic Influenzavirus A Male Chemokine viral immunology Integrin alpha1 Immunology CD8 T cells CD8-Positive T-Lymphocytes medicine.disease_cause Virus Memory T Cells Immune system Orthomyxoviridae Infections resident memory TRM Influenza A virus medicine Animals influenza A virus Immunology and Allergy Cytotoxic T cell Antigen-presenting cell Lung Cells Cultured Original Research Innate immune system biology Effector Granulocyte-Macrophage Colony-Stimulating Factor RC581-607 CD49a Mice Inbred C57BL Disease Models Animal Kinetics Phenotype polyfunctionality Host-Pathogen Interactions CD103 biology.protein Chemokines Immunologic diseases. Allergy Antibody Immunologic Memory CD8 |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| Popis: | CD8 T cell memory offers critical antiviral protection, even in the absence of neutralizing antibodies. The paradigm is that CD8 T cell memory within the lung tissue consists of a mix of circulating TEMcells and non-circulating TRMcells. However, based on our analysis, the heterogeneity within the tissue is much higher, identifying TCM, TEM, TRM, and a multitude of populations which do not perfectly fit these classifications. Further interrogation of the populations shows that TRMcells that express CD49a, both with and without CD103, have increased and diverse effector potential compared with CD49a negative populations. These populations function as a one-man band, displaying antiviral activity, chemokine production, release of GM-CSF, and the ability to kill specific targetsinvitro with delayed kinetics compared with effector CD8 T cells. Together, this study establishes that CD49a defines multiple polyfunctional CD8 memory subsets after clearance of influenza infection, which act to eliminate virus in the absence of direct killing, recruit and mature innate immune cells, and destroy infected cells if the virus persists.Contribution to the fieldProtection from previously seen infections requires specialized immune memory cells properly positioned throughout the body to combat the newly invading pathogen. In the case of re-exposure to influenza virus, CD8 T cells resident within the respiratory tract (TRM) are critical for eliminating the virus. Previously, TRMwere viewed as mostly homogenous, with a limited range of immune functions. In this study, lung TRMwere compared with circulating memory CD8 T cells transiently present within the lung, to define the breadth of their effector capabilities. Using TRMdefining surface proteins CD49a and CD103 to identify different memory CD8 T cell subsets, gene and protein expression were evaluated. In addition to demonstrating higher levels of diversity than previously reported, multiple polyfunctional subsets were identified. This polyfunctionality was primarily associated with cell populations expressing CD49a, and these cells produced multiple antiviral factors, chemokines to recruit other immune cells, a growth factor associated with improved antigen presenting cell function, and cytolytic granules. Functional assays further demonstrated killing of target cells by TRM. This study paints a more holistic, complete picture of the phenotype and functions of lung CD8 T cells after viral infection, revealing CD49a as a marker of cells with high effector capacity. |
| Databáze: | OpenAIRE |
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