title: Activated, cytotoxic CD8(+) T lymphocytes contribute to the pathology of asthma death.
abstract: 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-gamma) by CD8(+) T cells was higher in the AD group than the control group (p < 0.05). Furthermore, the IFN-gamma/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.
authors.affiliation: Department of Respiratory Medicine, James Connolly Memorial Hospital, Dublin, Ireland. sioosu@indigo.ie
authors.forename: S
authors.initials: S
authors.lastname: O'Sullivan
authors.forename: L
authors.initials: L
authors.lastname: Cormican
authors.forename: J L
authors.initials: JL
authors.lastname: Faul
authors.forename: S
authors.initials: S
authors.lastname: Ichinohe
authors.forename: S L
authors.initials: SL
authors.lastname: Johnston
authors.forename: C M
authors.initials: CM
authors.lastname: Burke
authors.forename: L W
authors.initials: LW
authors.lastname: Poulter
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D001344:Autopsy; D001706:Biopsy; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002423:Cause of Death; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology; D008875:Middle Aged; D054353:Perforin; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D012307:Risk Factors; D016037:Single-Blind Method; D014777:Virus Diseases / Q000150:complications / Q000175:diagnosis / Q000821:virology
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D015847:Interleukin-4; D007371:Interferon-gamma