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 -defi cient Tc1- or Tc2-CD8 effector cells responding to influenza pneumonia, The adoptive transfer of influenza hemagglutinin-specific Tc1 effecters afford ed protection and elicited only minimal impairment of lung function. IFN-ga mma -deficient Tc1 effector cells were equally protective, but were associa ted with an eosinophil influx and slightly more lung function impairment ea rly in the response. Relative to Tc1, Tc2 effector cells were less protecti ve, elicited an eosinophil influx and a greater impairment of lung function s. IFN-gamma -deficient Tc2 effector cells were not protective and were ass ociated with the severest impairment of lung function throughout the respon se, 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 inflammato ry response that resulted in more severe lung function impairment in the re cipients of either Tc1 or Tc2 IFN-gamma -deficient effector cells. Thus, du ring influenza infections, IFN-gamma production by the responding CD8 T cel ls is associated with effector cell recruitment and mitigation of the assoc iated inflammation and of the resulting impairment in lung functions but is not necessary for optimal protection.