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| ANDREA COOPER, PH.D. |
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Initiation of cellular responses in the lung. |
We have examined the initiation of migration from the lungs to the draining lymph node in response to bacterial (pathogen) stimulus. This migration is dependent upon IL-12p40, likely in the homodimer form. We also think that the expression of IL-10 in response to bacterial stimulus regulates the effect of the IL-12p40. Thus the balance between IL-12p40 and IL-10 in the lung dendritic cells may be the deciding factor in whether the dendritic cell migrates (with antigen) from the lung to the draining node and thereby initiates a cellular response.
Following delivery of Mycobacterium tuberculosis to the lung there is a profound delay before acquired cellular immunity is expressed in the lung (20 days). We can improve the timeframe to 15 days if mice are vaccinated but this is still a slow response. We have recently identified a population of vaccine-induced memory cells which reside in the lung and that are required for the expression of acquired cellular protection. These cells make IL-17 and initiate a chemokine response that allows IFN-?-producing memory cells to enter the lung. We are investigating whether modulation of these IL-17-producing cells will accelerate the kinetics of the protective response in the lung.
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