Pulmonary antigen encounter regulates the establishment of tissue-resident CD8 memory T cells in the lung airways and parenchyma
| Autor: | Sean R. McMaster, Timothy L. Denning, Alexander N. Wein, Jacob E. Kohlmeier, Sarah L. Hayward, Emily K. Cartwright, Paul Dunbar |
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| Rok vydání: | 2018 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte 0301 basic medicine Cellular immunity Immunology T cell memory Tissue-resident Respiratory Mucosa CD8-Positive T-Lymphocytes Lymphocyte Activation Article Integrin alpha1beta1 Mice 03 medical and health sciences Influenza A Virus H1N1 Subtype Orthomyxoviridae Infections Antigen Antigens CD Influenza Human Parenchyma medicine Animals Humans Immunology and Allergy Cytotoxic T cell Lectins C-Type Antigens Lung Cells Cultured Effector business.industry Vaccination T lymphocyte Viral Load respiratory system 3. Good health Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Influenza Vaccines Influenza virus business Immunologic Memory CD8 |
| Zdroj: | Mucosal immunology |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/s41385-018-0003-x |
| Popis: | Resident memory CD8 T (TRM) cells in the lung parenchyma (LP) and airways provide heterologous protection against influenza virus challenge. However, scant knowledge exists regarding factors necessary to establish and maintain lung CD8 TRM. Here we demonstrate that, in contrast to mechanisms described for other tissues, airway, and LP CD8 TRM establishment requires cognate antigen recognition in the lung. Systemic effector CD8 T cells could be transiently pulled into the lung in response to localized inflammation, however these effector cells failed to establish tissue residency unless antigen was present in the pulmonary environment. The interaction of effector CD8 T cells with cognate antigen in the lung resulted in increased and prolonged expression of the tissue-retention markers CD69 and CD103, and increased expression of the adhesion molecule VLA-1. The inability of localized inflammation alone to establish lung TRM resulted in decreased viral clearance and increased mortality following heterosubtypic influenza challenge, despite equal numbers of circulating memory CD8 T cells. These findings demonstrate that pulmonary antigen encounter is required for the establishment of lung CD8 TRM and may inform future vaccine strategies to generate robust cellular immunity against respiratory pathogens. |
| Databáze: | OpenAIRE |
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