Influenza Virus-Specific Cytotoxic T-Lymphocyte Activity in Fischer 344 Rat Lungs as a Method to Assess Pulmonary Immunocompetence: Effect of Phosgene Inhalation

Abstract

The use of viral and bacterial infectivity models has been valuable in the detection of toxicity following low-level inhalation exposures to environmental pollutants. These studies have traditionally been performed in the mouse model system where mortality was commonly reported as the end point of toxicity offering little information as to precise immunotoxicological mechanisms. This study utilized a rat influenza virus infectivity model to determine alterations in an important host antiviral immunologi-cal response following an acute 4.0-h exposure to 1.0 ppm phosgene. The effect on the specific antiviral immune response of the pulmonary cytotoxic T-lymphocyte (CTL) was determined as the measure of immunotoxicity. A significant suppression in the CTL response was detected 10 days postinfection, a time during which peak activity is normally detected in control rats. No alterations were detected in pulmonary cell populations at this time. CTL activity is an important antiviral immunological defense mechanism. CTL activity is the first specific immunological defense mechanism, and an inadequate CTL activity resulting from toxicant exposure could result in a significantly enhanced and prolonged pulmonary virus infection. Measurement of the influenza virus-specific CTL activity in the lung provides an important means to assess pulmonary immunotoxicology of inhaled compounds.