{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:14:03Z","timestamp":1793236443144,"version":"4.5.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lung CD8+ T cells might contribute to progression of chronic obstructive pulmonary disease (COPD) indirectly via IFN-\u03b3 production or directly via cytolysis, but evidence for either mechanism is largely circumstantial. To gain insights into these potential mechanisms, we analyzed clinically indicated lung resections from three human cohorts, correlating findings with spirometrically defined disease severity. Expression by lung CD8+ T cells of IL-18R and CD69 correlated with severity, as did mRNA transcripts for perforin and granzyme B, but not Fas ligand. These correlations persisted after correction for age, smoking history, presence of lung cancer, recent respiratory infection, or inhaled corticosteroid use. Analysis of transcripts for killer cell lectin-like receptor G1, IL-7R, and CD57 implied that lung CD8+ T cells in COPD do not belong to the terminally differentiated effector populations associated with chronic infections or extreme age. In vitro stimulation of lung CD8+ T cells with IL-18 plus IL-12 markedly increased production of IFN-\u03b3 and TNF-\u03b1, whereas IL-15 stimulation induced increased intracellular perforin expression. Both IL-15 and IL-18 protein expression could be measured in whole lung tissue homogenates, but neither correlated in concentration with spirometric severity. Although lung CD8+ T cell expression of mRNA for both T-box transcription factor expressed in T cells and GATA-binding protein 3 (but not retinoic acid receptor-related orphan receptor \u03b3 or \u03b1) increased with spirometric severity, stimulation of lung CD8+ T cells via CD3\u03b5-induced secretion of IFN-\u03b3, TNF-\u03b1, and GM-CSF, but not IL-5, IL-13, and IL-17A. These findings suggest that the production of proinflammatory cytokines and cytotoxic molecules by lung-resident CD8+ T cells contributes to COPD pathogenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.1000006","type":"journal-article","created":{"date-parts":[[2010,4,28]],"date-time":"2010-04-28T23:16:58Z","timestamp":1272496618000},"page":"6504-6513","source":"Crossref","is-referenced-by-count":117,"title":["Cytotoxic Potential of Lung CD8+ T Cells Increases with Chronic Obstructive Pulmonary Disease Severity and with In Vitro Stimulation by IL-18 or IL-15"],"prefix":"10.1093","volume":"184","author":[{"given":"Christine M","family":"Freeman","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Medicine Section"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MeiLan K","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical 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