Am. J. Respir. Crit. Care Med., Volume 164, Number 4, August 2001, 560-564

Activated, Cytotoxic CD8⁺ T Lymphocytes Contribute to the Pathology of Asthma Death

S. O'SULLIVAN, L. CORMICAN, J. L. FAUL, S. ICHINOHE, S. L. JOHNSTON, C. M. BURKE, and L. W. POULTER

Department of Respiratory Medicine, James Connolly Memorial Hospital, Dublin, Ireland; National Heart and Lung Institute at St. Mary's, Imperial College School of Medicine, London; and Department of Clinical Immunology, Royal Free and University College Hospital Medical School, London, United Kingdom

This study investigates the presence of CD8⁺ T lymphocytes and their possible association with viral infection in bronchi of victims of fatal asthma. Postmortem samples from the peribronchial region of the lung were obtained from seven patients who died an asthma death (AD), seven asthmatic patients who died of unrelated causes (AUC), and seven postmortem cases with no history of lung disease (control subjects). Using immunohistochemical techniques, the CD8⁺ cytotoxic T-cell population in peribronchial tissue was characterized in three patient groups. The percentage of CD8⁺ cells expressing the activation marker CD25 was higher in the AD group than in both the AUC and control groups (11.91 ± 1.92% versus 3.93 ± 1.63% and 1.09 ± 0.56%, respectively (p < 0.001). Perforin expression, a marker of cytotoxicity, was highest in the AD group (9.16 ± 1.5%) compared with 1.39 ± 0.9; 1.8 ± 0.6% in the AUC and control groups respectively (p < 0.001). Expression of interleukin-4 (IL-4) and interferon gamma (IFN-) by CD8⁺ T cells was higher in the AD group than the control group (p < 0.05). Furthermore, the IFN-/IL-4 ratio in the AD group was less than half that of the control group (1.46 ± 0.2 versus 3.2 ± 0.1; p = 0.02). Using polymerase chain reaction (PCR), viral genome for rhinovirus (RV) was detected in lung tissue from three of the seven cases in the AD group. Two of these cases also had detectable respiratory syncytial virus (RSV). Viral genome for RSV was detected in five of the AUC group and in one of these cases, RV was also detected. No viral genome was detected in the lungs of the control group. In conclusion, this study provides novel evidence of an aberrant CD8⁺ T-cell population, possibly in response to viral infection in subjects who die of acute asthma.

Keywords: asthma death; virus; CD8⁺ T lymphocytes

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