Type II Pneumocyte-CD8+ T-Cell Interactions . Relationship between Target Cell Cytotoxicity and Activation

CD8+ T-cell responses play an important role in the clearance of respiratory virus infection, but may also contribute to lung injury in the process. The effector mechanisms involved in viral clearance and associated lung injury include both cytolytic and noncytolytic effector functions. Previously w...

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Bibliographic Details
Published in:	American journal of respiratory cell and molecular biology Vol. 25; no. 3; pp. 362 - 369
Main Authors:	Zhao, Min Q, Amir, Mana K, Rice, Ward R, Enelow, Richard I
Format:	Journal Article
Language:	English
Published:	United States Am Thoracic Soc 01-09-2001 American Thoracic Society
Subjects:	Animals Antigen Presentation Antigens, Viral - immunology CD8-Positive T-Lymphocytes - immunology Cells, Cultured Chemokine CCL2 - metabolism Cytotoxicity, Immunologic Epithelial Cells - immunology Epitopes - immunology Genes, Reporter Histocompatibility Antigens Class I - chemistry Histocompatibility Antigens Class I - metabolism Influenza A virus - immunology Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Mice Mice, Inbred BALB C NF-kappa B - genetics NF-kappa B - metabolism Orthomyxoviridae Infections - immunology Peptides - immunology Peptides - pharmacology Perforin Pore Forming Cytotoxic Proteins Pulmonary Alveoli - cytology Pulmonary Alveoli - immunology Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Tumor Necrosis Factor-alpha - pharmacology Viral Proteins - immunology
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Summary:	CD8+ T-cell responses play an important role in the clearance of respiratory virus infection, but may also contribute to lung injury in the process. The effector mechanisms involved in viral clearance and associated lung injury include both cytolytic and noncytolytic effector functions. Previously we have shown that CD8+ T-cell recognition of alveolar epithelial cells triggers chemokine expression by the epithelial cell and that this plays an important role in the inflammatory infiltration that ensues in the context of T cell-mediated injury (Zhao and colleagues, J. Clin. Invest. 2000;106:R49-R58). In the present study we sought to understand the relationship between alveolar cell cytotoxicity and chemokine expression, both of which occur as a result of CD8+ T-cell antigen recognition. Alveolar epithelial cells efficiently process and present overlapping viral epitopes, and CD8+ T-cell recognition of these class I major histocompatibility complex-restricted epitopes resulted in cytotoxicity of the alveolar cells by both wild-type and perforin-deficient T cells. However, the contribution of perforin-mediated lysis to the total cytotoxicity of alveolar cells by CD8+ T cells was minimal, and the majority of the lysis was attributable to tumor necrosis factor-alpha expressed by the T cell. CD8+ T-cell recognition also led to activation of nuclear factor-kappaB in the alveolar epithelial target cells, at levels inversely proportional to the effector/target (E:T) ratio. Finally, at varying E:T ratios, we demonstrated an inverse relationship between alveolar cell cytotoxicity and monocyte chemotactic protein-1 expression, both of which occur as a result of T-cell recognition. These findings may have important ramifications in understanding the relationship between viral clearance and lung injury.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1044-1549 1535-4989
DOI:	10.1165/ajrcmb.25.3.4476