Friendly Fire within the Lungs
HZI researchers show how immune cells mistakenly attack the lungs in chronic obstructive pulmonary disease patients
Cigarette smoke or a high level of exposure to dust damages our lungs – cells of the immune system are activated within the sensitive respiratory tract and by mistake can attack the healthy pulmonary tissue. This so-called auto-immune reaction can lead to serious chronic inflammations. In a current study researchers at the Helmholtz-Centre for Infection Research (HZI) in Braunschweig succeeded in describing more exactly the role of those particular immune cells that are involved in the development of chronic obstructive pulmonary disease. The results are now being published by the researchers in the current edition of The Journal of Immunology.
“Smoking or harmful exposure to dust makes up the initial steps that lead to formation of an inflammatory environment in the alveoli,” says Dr. Dunja Bruder, head of the research group “Immune Regulation” at HZI. “If the lung is continuously exposed to harmful substances, an inflammatory process that is typical for auto-immune diseases is subsequently set in motion,” adds the scientist. “Cells from the immune system become activated, multiply and then mistakenly attack the body.“ Smoking is recognized as a primary trigger for chronic obstructive pulmonary disease (COPD) – in short, ‘smokers’ cough’. However, COPD is also found in workers that were exposed to high level of dust or fume. Furthermore, in Third World countries women are mainly affected: Here, a continuous exposure to dust from smouldering hearths in closed rooms is a common cause. In recent years increasing scientific findings indicate that the disease can be considered as an auto-immune disease.
Dunja Bruder’s research team has been evaluating for a number of years how the cells of the Pulmonary alveoli communicate with the cells of the immune system. In the current study, the immunologists were able to more specifically describe the role of immune cells that trigger COPD. This involves so-called killer T cells, which naturally destroy virus infected cells. In this manner the immune system is usually quite successful in combating infections. In the COPD case however the persistent provocation of the immune system in the lung leads to a false reaction – the killer T cells attack the body’s own lung cells.
In order to better understand the behaviour of killer T cells and to be able to intervene against the errant immune system, the researchers Dr. Milena Tosiek and Dr. Marcus Gereke from Dr. Dunja Bruder’s team simulated the events in a completely novel mouse model. “The mice carry a protein of the influenza virus on the surface of their alveoli. They also have killer T cells that are able to recognize precisely this viral protein and therefore attack the lung cells. As a result, the mice develop a chronic lung inflammation that is triggered by the killer T cells,” the researcher Dr. Marcus Gereke reports. The researchers isolated the disease-causing cells from the inflamed lung in order to analyse them in more detail.
The results surprised the researchers – many immune cells in the inflamed tissue are not at all involved in destruction of the lung cells. Most killer T cells simply “ignored” the lung cells. Only a few cells reacted – but all the more fiercely and with fatal consequences.
“This shows how important the healthy balance of the immune cells is,” says Dr. Dunja Bruder. “Even a small quantity of erroneously activated killer T cells could lead to considerable tissue destruction.”
The scientists from Braunschweig are currently carrying out intensive research on the control mechanisms that could circumvent complete destruction of the pulmonary alveoli. “We hope that the understanding of those mechanisms will then lead to a further improvement of COPD treatment in the future,” says Dr. Dunja Bruder.
CD+4CD25+Foxp3+ Regulatory T Cells Are Dispenbsable for Controlling CD8+ T Cell-mediated Lung Inflammation. Tosiek MJ, Gruber AD, Bader SR, Mauel S, Hymann H-G, Prettin S, Tschernig T, Buer J, Gereke M, Bruder D. The Journal of Immunology, 2011, Jun 1. 186(11):6106-18.