title: T lymphocyte-mediated changes in airway smooth muscle responsiveness are attributed to induced autocrine release and actions of IL-5 and IL-1beta.
abstract: BACKGROUND
  Bidirectional stimulatory cross-talk was recently found to exist between activated T cells and airway smooth muscle (ASM) cells, a process that involves coligation of specific cellular adhesion-costimulatory molecules that results in the induction of proasthmatic-like changes in ASM responsiveness.
  
  
  OBJECTIVE
  The present study examined whether the cooperative intercellular signaling between activated T cells and ASM cells is coupled to the induced expression and actions of IL-5 and IL-1beta.
  
  
  METHODS
  Agonist-induced constrictor and relaxant responses were examined in rabbit ASM segments exposed to resting and anti-CD3-activated T cells in the absence and presence of either an anti-IL-5 receptor mAb or the recombinant human IL-1 receptor antagonist. In addition, mRNA and protein expression of IL-5 and IL-1beta were assayed under control and anti-CD3-stimulated conditions.
  
  
  RESULTS
  Relative to inactive T cells, incubation of ASM tissues with anti-CD3-activated T cells induced proasthmatic-like changes in agonist-mediated ASM responsiveness. This T cell-induced perturbation in ASM responsiveness was ablated by pretreating the tissues with either an anti-IL-5 receptor mAb or IL-1 receptor antagonist. Moreover, exposure of ASM cells to anti-CD3-activated T cells elicited an initial increased mRNA expression and release of IL-5, followed by an enhanced expression and release of IL-1beta, and the induced release of these cytokines was prevented in ASM cells that were pretreated with an anti-IL-5 receptor mAb.
  
  
  CONCLUSIONS
  Collectively, these observations provide new evidence demonstrating that exposure of naive ASM cells to activated T cells induces the sequential release of IL-5 and IL-1beta from the ASM cells and that the latter cytokines act in an autocrine manner to elicit the proasthmatic phenotype of altered ASM responsiveness.
authors.affiliation: Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Russell
authors.initials: R
authors.lastname: Whelan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Leiter
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kim
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: Donald
authors.initials: D
authors.lastname: Campbell
authors.forename: Michael M
authors.initials: MM
authors.lastname: Grunstein
mesh_terms: D000328:Adult; D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology*; D015848:Interleukin-5 / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology*; D011817:Rabbits; D013601:T-Lymphocytes / Q000502:physiology*; D014132:Trachea / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D015848:Interleukin-5