Cellular immunity and lung injury in respiratory virus infection

Abstract

Respiratory virus infection may result in considerable lung injury, and host immune responses may be an important contributor to this. Important factors that determine the magnitude of immunopathologic tissue damage include the degree of distal distribution of infection into alveolar cells, the overall viral load, the magnitude of the T-cell responses, the effector mechanisms employed by the T cells, and regulatory mechanisms which may come into play. CD8+ T cells are important contributors to viral clearance, utilizing contact-dependent effector functions (perforin and CD95L) as well as IFN-gamma and TNF-alpha. IFN-gamma and TNF-alpha are primary perpetrators of T-cell-mediated lung injury, with TNF as the major contributor. It is not entirely clear at present the degree to which injury is a necessary consequence of host defense to respiratory virus infection, though there are tantalizing bits of evidence to the contrary. In murine models, TNF plays only a minor role in antiviral activity and clearance of laboratory strains of RSV and influenza. In the event of a pandemic with a highly virulent virus, intervention directed at TNF-alpha should be given consideration, as this may be most likely to provide protection against severe lung injury at the lowest cost to viral clearance.