We are interested in the fundamental processes that regulate immune responses to viral infections. We are particularly interested in understanding how T cells respond to viruses because primary adaptive responses as well as memory require both CD4+ and CD8+ T cells. Many types of infectious pathogens (e.g., bacteria, viruses, mycobacteria, etc.) induce the secretion of an important innate cytokine, IL-12. The effects of IL-12 in regulating CD4+ Th1 development and CD8+ cytotoxic activity have been well established. In addition to IL-12, viral infections also induce the secretion of type I interferon (IFN-alpha/beta). IFN-alpha/beta is a key innate cytokine that is secreted by virus-infected cells, and this cytokine has the potential to regulate the development of responding CD4+ and CD8+ T cells. However, unlike the effects of IL-12, the role of IFN-alpha/beta in adaptive immune responses has not been extensively characterized. The goal of our research is to understand how IFN-alpha/beta regulates effector and memory functions of T cells that are uniquely suited to combating viral infections. To this end, we are attacking the problem from 2 related angles. First, we are characterizing the specific effector and memory functions of human T cells that are induced by IFN-alpha/beta. Second, we use genetically defined transgenic and knock-out mouse strains to probe the function of IFN-alpha/beta during T cell responses to virus infection in vivo. These two avenues of research will allow us to thoroughly examine anti-viral responses that are directly applicable to infections in humans. The ultimate goal from these studies is to apply this knowledge toward the design of more effective and safe vaccines.
RESEARCH INTERESTS
T cell development
Cytokine signaling
Cytokine gene regulation
Host/pathogen interactions
RECENT PUBLICATIONS
J. David Farrar, Wenjun Ouyang, Max Lohning, Mario Assenmacher, Andreas Radbruch, Osami Kanagawa, and Kenneth M. Murphy, "An instructive component in T helper cell type 2 (Th2) development mediated by GATA-3" Journal of Experimental Medicine, 193:643-649, March 2001
Meredith E. Persky, Kenneth M. Murphy, and J. David Farrar, "IL-12, but not IFN-alpha, promotes STAT4 activation and Th1 development in murine CD4+ T cells expressing a chimeric murine/human Stat2 gene" J. Immunol., 174:294-301, January 2005
Tyler, D. R., M. E. Persky, L. A. Matthews, S. Chan, and J. D. Farrar, "Pre-assembly of STAT4 with the human IFN-alpha/beta receptor-2 subunit is mediated by the STAT4 N-domain" Molecular Immunology, 44:1874-1882, January 2007
Hilario J. Ramos, Ann M. Davis, Thaddeus C. George, and J. David Farrar, "IFN-alpha is not sufficient to drive Th1 development due to lack of stable T-bet expression" The Journal of Immunology, 179:3792-3803, September 2007
A. M. Davis, K. A. Hagan, L. A. Matthews, G. Bajwa, M. A. Gill, M. Gale Jr., J. D. Farrar, "Blockade of virus infection by human CD4+ T cells via a cytokine relay network" Journal of Immunology, 180:6923-6932, May 2008
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