title: CD4+ T lymphocytes mediate acute pulmonary ischemia-reperfusion injury.
abstract: OBJECTIVE
  Postischemic reperfusion of the lung triggers proinflammatory responses that stimulate injurious neutrophil chemotaxis. We hypothesized that T lymphocytes are recruited and activated during reperfusion and mediate subsequent neutrophil-induced lung ischemia-reperfusion injury.
  
  
  METHODS
  An in vivo mouse model of lung ischemia-reperfusion injury was used. C57BL/6 mice were assigned to either the sham group (left thoracotomy) or 7 study groups that underwent 1-hour left hilar occlusion followed by 1 to 24 hours of reperfusion. After in vivo reperfusion, the lungs were perfused ex vivo with buffer whereby pulmonary function was assessed. Lung vascular permeability, edema, neutrophil accumulation, and cytokine/chemokine production (tumor necrosis factor alpha, interleukin 17, CCL3, and CXCL1) were assessed based on Evans blue dye leak, wet/dry weight ratio, myeloperoxidase level, and enzyme-linked immunosorbent assay, respectively.
  
  
  RESULTS
  A preliminary study showed that 2 hours of reperfusion resulted in greater pulmonary dysfunction than 1 or 24 hours of reperfusion. The 2-hour reperfusion period was thus used for the remaining experiments. Comparable and significant protection from ischemia-reperfusion injury-induced lung dysfunction and injury occurred after antibody depletion of neutrophils or CD4(+) T cells but not CD8(+) T cells (P < .05 vs immunoglobulin G control). Lung ischemia-reperfusion injury was proportional to the infiltration of neutrophils but not T cells. Moreover, pulmonary neutrophil infiltration and the production of CXCL1 (KC) were significantly diminished by CD4(+) T-cell depletion but not vice versa.
  
  
  CONCLUSIONS
  Both CD4(+) T lymphocytes and neutrophils accumulate during reperfusion and contribute sequentially to lung ischemia-reperfusion injury. The data suggest that neutrophils mediate ischemia-reperfusion injury; however, CD4(+) T cells play a critical role in stimulating chemokine production and neutrophil chemotaxis during ischemia-reperfusion injury.
authors.affiliation: Department of Surgery, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Zequan
authors.initials: Z
authors.lastname: Yang
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.forename: Irving L
authors.initials: IL
authors.lastname: Kron
authors.forename: Victor E
authors.initials: VE
authors.lastname: Laubach
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000276:immunology*