Pediatr Allergy Respir Dis.  2000 Dec;10(4):279-289.

CD4+ T Helper Cells Engineered to Produce IL-10 Reverse Allergen-induced Airway Hyperreactivity and Inflammation

• Oh JW
• Dekruyff R
• Umetsu D

Abstract

PURPOSE
Asthma is characterized by airway hyperreactivity to a variety of specific and nonspecific stimuli, by chronic airway inflammation with pulmonary eosinophilia, by mucus hypersecretion, and by increased serum IgE levels. T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanism that inhibit Th2 cell function in vivo are not well understood.
METHODS
Using gene therapy, Th-cell lines were transferred intravenously into histocompatible SCID or OVA immunized BALB/c mice. Airway responsiveness was assessed by methacholine-induced airflow obstruction from conscious mice placed in a whole-body plethysmograph. Pulmonary airflow obstruction was measured by enhanced pause (Penh).
RESULTS
We demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express IL-10 abolished airway hyperreactivity induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. The inhibitory effect of IL-10 transduced Th cells was antigen-specific and was reversed by neutralization of IL-10.
CONCLUSION
Our results demonstrate that IL-10 transduced CD4+ Th cells in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity.

Keyword

IL-10; Th2 cells; Airway hyperreactivity

MeSH Terms

Animals
Asthma
Genetic Therapy
Immunoglobulin E
Inflammation*
Interleukin-10*
Mice
Mucus
Ovum
Pulmonary Eosinophilia
Respiratory Mucosa
T-Lymphocytes, Helper-Inducer*
Th2 Cells
Immunoglobulin E
Interleukin-10