Production of interferon-gamma by influenza hemagglutinin-specific CD8 effector T cells influences the development of pulmonary immunopathology.
This study examined the inflammation, lung function impairment, and immune protection associated with either wild-type or interferon (IFN)-gamma-deficient Tc1- or Tc2-CD8 effector cells responding to influenza pneumonia. The adoptive transfer of influenza hemagglutinin-specific Tc1 effectors afforded protection and elicited only minimal impairment of lung function. IFN-gamma-deficient Tc1 effector cells were equally protective, but were associated with an eosinophil influx and slightly more lung function impairment early in the response. Relative to Tc1, Tc2 effector cells were less protective, elicited an eosinophil influx and a greater impairment of lung functions. IFN-gamma-deficient Tc2 effector cells were not protective and were associated with the severest impairment of lung function throughout the response, an accumulation of neutrophils, and extensive pulmonary vasculitis and alveolar hemorrhaging. Deletion of IFN-gamma was associated with a delay in effector cell recruitment and the elicitation of a more intense inflammatory response that resulted in more severe lung function impairment in the recipients of either Tc1 or Tc2 IFN-gamma-deficient effector cells. Thus, during influenza infections, IFN-gamma production by the responding CD8 T cells is associated with effector cell recruitment and mitigation of the associated inflammation and of the resulting impairment in lung functions but is not necessary for optimal protection.
Wiley
J A
JA
Trudeau Institute, Saranac Lake, New York 12983, USA. jwiley@trudeauinstitute.org
Cerwenka
A
A
Harkema
J R
JR
Dutton
R W
RW
Harmsen
A G
AG
D000818:Animals; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D006389:Hemagglutinins, Viral / Q000276:immunology; D016219:Immunotherapy, Adoptive; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D008171:Lung Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000821:virology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012119:Respiration; D018800:Thy-1 Antigens / Q000276:immunology; D013997:Time Factors
D016827:CD8 Antigens; D016207:Cytokines; D006389:Hemagglutinins, Viral; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens; D007371:Interferon-gamma; D010100:Oxygen