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ANDREA COOPER, PH.D.
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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ROBERT NORTH, PH.D. MARCIA A. BLACKMAN, PH.D. TIMOTHY SELLATI, PH.D. MARKUS MOHRS, PH.D. LAWRENCE L. JOHNSON, PH.D. ANDREA COOPER, PH.D. ELIZABETH LEADBETTER, PH.D. ALEXEI TUMANOV, M.D., PH.D. JR-SHIUAN LIN, PH.D. WILLIAM W. REILEY, PH.D. RON GOLDFARB, PH.D. SUSAN L. SWAIN, PH.D. RICHARD W. DUTTON, PH.D. DAVID WOODLAND, PH.D. GARY WINSLOW, PH.D. LAURA HAYNES, PH.D.