T lymphocyte-mediated changes in airway smooth muscle responsiveness are attributed to induced autocrine release and actions of IL-5 and IL-1beta.
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.
Hakonarson
Hakon
H
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.
Whelan
Russell
R
Leiter
Jennifer
J
Kim
Cecilia
C
Chen
Mei
M
Campbell
Donald
D
Grunstein
Michael M
MM
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*
D007375:Interleukin-1; D015848:Interleukin-5