Abstracts (complete list) - Wissenschaft Online

Marcus Gereke, Jan Buer, Dunja Bruder
Collaboration of the innate and adaptive immune system
leads to immunological tolerance in the lung
The lung with its exposed position has many tolerogenic properties to avoid an
immunological collapse due to infection and inflammation. However, little is known
about synergisms of innate and adaptive immunity in inducing peripheral tolerance in
the lung. To get further immunological and molecular insights in the mechanisms
underlying peripheral tolerance induction in the lung, CD4+ T cell reactivity to a lungspecific
antigen was studied by transgenic expression of hemagglutinin (HA) in alveolar
type II epithelial cells. Concomitant expression of HA and a MHC class II-restricted T cell
receptor specific for HA in double transgenic mice resulted in a severe immunemediated
interstitial lung disease. Despite aggressive and rapid progression of
inflammation in lungs of young mice, pulmonary inflammation reached a plateau state
in elder mice, suggesting the induction of peripheral tolerance mechanisms. Intensive
characterization of self-reactive CD4+ T cells isolated from the inflamed lung suggested
the induction of functional regulatory T cells at the site of inflammation. Epithelial cells
represent a part of the innate immune system and play an important role supporting
immune responses. Isolation of antigen-expressing alveolar type II epithelial cells (AEC
II) enabled us to directly demonstrate that these particular cells are capable to induce
antigen-specific T cell proliferation. Moreover, AEC II from diseased mice have a
reduced capacity to stimulate naïve self-reactive CD4+ T cells and exhibit broad
changes in their gene expression profile compared to AEC II derived from healthy
control mice. Furthermore, AEC II from the inflamed lung secrete soluble factors that
down modulate T cell proliferation. Data obtained by extensive functional and molecular
characterization suggest an important role of alveolar type II epithelial cells for the
induction of T cell tolerance and immune regulation in the lung and point at a close
collaboration between the innate and adaptive immune system.