T lymphocyte-mediated changes in airway smooth muscle responsiveness are attributed to induced autocrine release and actions of IL-5 and IL-1beta

J Allergy Clin Immunol. 2002 Oct;110(4):624-33. doi: 10.1067/mai.2002.128529.


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.

Conclusion: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Autocrine Communication / physiology*
  • Cells, Cultured
  • Humans
  • In Vitro Techniques
  • Interleukin-1 / physiology*
  • Interleukin-5 / physiology*
  • Intracellular Membranes / metabolism
  • Lymphocyte Activation / physiology
  • Male
  • Muscle, Smooth / physiology*
  • Rabbits
  • T-Lymphocytes / physiology*
  • Trachea / physiology*


  • Interleukin-1
  • Interleukin-5