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Kevin L. Legge, Ph.D.

Ph.D., University of Tennessee-Knoxville, 2000

Assistant Professor of Pathology and Microbiology Campus address: 1036 ML Mailing address: 25 S Grand Ave 1036 Medical Laboratories Iowa City, IA 52242 Phone: 319-335-6744

Pulmonary Immunology

My laboratory is focused upon determining the role that respiratory dendritic cells (rDC) play in initiating and regulating the T cell responses to pulmonary pathogens, in particular influenza virus. We have shown that influenza infections trigger a rapid but transient migration of mature rDC from the lungs to the lymph nodes. This halt in rDC migration results in a suppression of pulmonary T cell responses to subsequent infections and therefore may contribute to the high preponderance of secondary bacterial pneumonias that occur following respiratory virus infections. However the retention of the dendritic cells in the lungs importantly allows local peripheral interactions of the dendritic cells with effector T cells - therein boosting pulmonary CD8 T cell responses and allowing viral clearance and recovery from infection.

The laboratory is also focused on delineating the factors that control rDC programming in the lungs and how the type and degree of the pulmonary infection is translated by rDC into changes into different activation of T cells within the lymph nodes. Our work has shown that the degree of influenza virus infection leads to diverse programming of rDC which in turn results in differential DC cytokine production in the lymph nodes and distinct levels of T cell fitness.

Additional studies are determining how chronic alcohol consumption increases the severity of pulmonary infections. Alcoholics are known to be at increased risk for severe pulmonary infections, yet the underlying changes in immunity that correspond with the increased disease are poorly understood. Our current work suggests that alterations in CD8 T cell responses, neutrophilia, edema, and pulmonary dendritic cells all contribute to the increased severity. Further we have shown that exposure to ethanol during fetal development leads to long term increases in susceptibility to influenza virus infections.

Overall the goals of our studies are to determine which DC-derived factors and interactions are necessary to induce protective T cell responses during pathogen infections of the lungs. This knowledge will be important in the rational design of methods to alter respiratory immunopathology, improve vaccinations, and boost T cell responses in the lungs to influenza virus and other pulmonary pathogens.

Recent publications

McGill, J., Van Rooijen, N., and Legge, K.L. Lung recruited dendritic cells are necessary for complete activation of pulmonary influenza-specific CD8 T cell responses. Journal of Experimental Medicine 205:1635, 2008.

Meyerholz, D.K., Edsen-Moore, M., McGill, J., Coleman, R.A., Cook, R.T., and Legge, K.L. Chronic Alcohol Consumption Increases the Severity of Murine Influenza Virus Infections. The Journal of Immunology 181:641, 2008.

Brincks, E.L., Katewa, A., Kucaba, T.A., Griffith, T.S., and Legge, K.L. CD8 T cells Utilize TNF-related apoptosis –inducing ligand (TRAIL) to control influenza virus infection. The Journal of Immunology, 181:4918, 2008.

McGill, J., and Legge, K.L. The Cutting Edge: Contribution of local proliferation of CD8 T cells within the lungs to the magnitude of the influenza-specific CD8 T cell response to influenza-virus infections. The Journal of Immunology-In Press, 2009.