Fewer CTL, not enhanced NK cells, are sufficient for viral clearance from the lungs of immunocompromised mice.
Activation of the aryl hydrocarbon receptor (AhR) causes numerous defects in anti-viral immunity, including suppressed CTL generation and impaired host resistance. However, despite a reduced CTL response, mice that survive infection clear the virus. Therefore, we examined the contribution of NK cells and pro-inflammatory cytokines to viral clearance in influenza virus-infected mice exposed to TCDD, the most potent AhR agonist. Infection caused transient increases in pulmonary TNFalpha, IL-1, and IFNalpha/beta levels, but neither the kinetics nor magnitude of this response was affected by AhR activation. No IL-18 was detected at any time point examined. Exposure to TCDD enhanced NK cell numbers in the lung but did not affect their IFNgamma production. Furthermore, depletion of NK cells did not alter anti-viral cytolytic activity. In contrast, removal of CD8+ T cells ablated virus-specific cytolytic activity. These results demonstrate that the pulmonary CTL response to influenza virus is robust and few CTL are necessary for viral clearance.
Neff-LaFord
Haley D
HD
Department of Pharmaceutical Sciences and the Pharmacology/Toxicology Graduate Program, College of Pharmacy, Washington State University, Pullman, WA 99164, USA.
Vorderstrasse
Beth A
BA
Lawrence
B Paige
BP
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016827:CD8 Antigens / Q000378:metabolism; D005260:Female; D009980:Influenza A virus / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013723:Teratogens / Q000378:metabolism
D016827:CD8 Antigens; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; D007371:Interferon-gamma