Functional impairment of cytotoxic T cells in the lung airways following respiratory virus infections.
We investigated the differentiation phenotype and function of virus-specific and non-specific CTL that were recruited to the lung parenchyma and the bronchoalveolar space after respiratory virus infections. Soon after virus elimination, we observed functional impairment of CTL isolated from the airways in their ability to produce IFN-gamma and TNF-alpha and to lyse target cells. Impaired cytotoxicity was due to a reduced content of granzyme B and a reduced ability to mobilize lytic granules. This impairment in effector functions (a) was largely restricted to CTL in the lung airways, (b) affected both CTL specific for the infecting virus as well as those that were recruited non-specifically to the inflamed lung, (c) was independent of contact between CTL and their specific viral antigen, (d) was not restricted to terminally differentiated CTL but also affected resting memory CTL and (e) could be elicited by both respiratory syncytial virus and influenza virus and thus seemed to be largely independent of the infecting virus. These observations suggest that functional impairment of antiviral T cells in the lung is not the consequence of a viral escape strategy. It may rather result from the particular milieu in the bronchoalveolar space and reflect a host mechanism to prevent excessive pulmonary inflammation.
Vallbracht
Simone
S
Children's Hospital, University of Freiburg, Germany.
Unsöld
Heike
H
Ehl
Stephan
S
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D015550:Cell Degranulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D053804:Granzymes; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000821:virology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000821:virology*; D012697:Serine Endopeptidases / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases