Rapid recovery of lung histology correlates with clearance of influenza virus by specific CD8+ cytotoxic T cells

Abstract

Previous studies have shown that influenza nucleoprotein (NP)-specific cytotoxic T-cell clones do not prevent influenza infection of mice but lead to a more rapid viral clearance and recovery of the host. Here we examine the histology of the lung to see if viral clearance by cytotoxic T cells (Tc) correlates with recovery of pulmonary pathology or if it is in any way deleterious. Intransasal (i.n.) A/X31 virus infection of BALB/c mice produces lung tissue changes lasting 8-10 days in BALB/c mice, with the most severe abnormalities appearing between Days 4 and 6 (e.g. loss of epithelium, airway obliteration, peribronchiolar and perivascular cell accumulation). The transfer of Tc clone T9/13 into i.n.-infected BALB/c mice induces a transient enhanced loss of epithelium on Day 4, while by Day 6 epithelial abnormalities are much reduced in the lung compared to control infected mice. This correlates with a significant reduction in lung virus titres by Day 6; by Day 8 virus is cleared in Tc recipients and lung histology is normal. Another Tc clone (T5/5) with greater cytolytic activity resulted in significant recovery of the lung tissues by Day 4. Tc clones also resulted in enhanced perivascular infiltration of cells and variation in the infiltrating cell type. Quantification in our system required careful attention to the level of the airway assessed. These histological findings showing an enhanced tissue recovery support the previous assessment of reduced lung viral levels following the transfer of Tc cells, and show that a transient increase in lung pathology can occur.