Body's defense mechanism worsens asthma symptoms

MUHC scientists have discovered that our body's own defense mechanism causes some of the most serious asthma symptoms. The study by MUHC researchers Dr. David Ramos-Barbón, Dr. Elizabeth Fixman and Dr. James Martin, published in a recent issue of Journal of Clinical Investigation (JCI), reveals that T lymphocytes--our body's defense cells--are responsible for the airway thickening, which increases the chances of a dangerous asthma attack. The discovery provides hope that new treatments might be developed to combat the disease, which currently has no cure.

Asthma symptoms are triggered by two factors: inflammation of the airways in the lungs, and thickening of airway muscle in the bronchi--an irreversible condition that doctors refer to as airway remodeling. Certain allergens--commonly dust and animal hair--can trigger inflammation, but the causes of airway remodeling (and the link between the two) have remained a mystery. MUHC researchers have now discovered that remodeling is actually caused by T lymphocytes--part of our body's own defense mechanism. "T lymphocytes are the traffic cops of the cellular world," says Dr. Ramos-Barbón. Where antigens are present, T lymphocytes can be found directing the body's defense mechanism, which in the case of asthmatics results in airway remodeling. "This is a natural response designed to protect the body from disease," notes Dr. Ramos-Barbón. "But in this case it actually promotes conditions that favour asthma, leading to increased symptoms such as coughing and difficulty breathing.

To make their discovery, researchers at the MUHC removed T lymphocytes from asthmatic rats, made them fluorescent by adding a jellyfish gene, and then transplanted them into non-asthmatic rats. "The fluorescence allowed us to track the movement of the T lymphocytes and determine their effect on the non-asthmatic rats," says Dr. Ramos-Barbón. Researchers were surprised to discover that the T lymphocytes moved directly to--and infiltrated--the airway walls of the non-asthmatic rats, causing extensive remodeling. Moreover, researchers discovered that the T lymphocytes must be in direct contact with the cells of the airway wall in order to cause remodeling.

"The next step is to develop mechanisms to interrupt this process and combat asthma," says Dr. Ramos-Barbón, who was presented the Eldon R. Smith Award for this research at the inaugural National Research Forum for Young Investigators in Circulatory and Respiratory Health, a major training and educational initiative of the CIHR Institute of Circulatory and Respiratory Health.

"This discovery is particularly exciting because it provides insight as to how the body's own CD4 T lymphocytes cause the thickening of the airway muscle, which increases the chances of a dangerous asthma attack. This research opens up new ways to prevent and treat asthma and its complications," said Dr. Bhagirath Singh, Scientific Director of CIHR's Institute of Infection and Immunity. "Continued research is key to advancements and hope for new diagnostic tests and treatments."

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August 11, 2005