Leo Lefranšois, Ph.D.
Department of Immunology Chairman
University of Connecticut Health Center
Department of Immunology
263 Farmington Avenue
Farmington, CT 06030-1319
The main focus of my research is to understand the immune response against microbial infections. Our work entails analysis of the CD8 and CD4 T cell immune response from the earliest times after response initiation through to the development of long-term immunological memory. The goal of these studies is to understand the cellular and molecular controllers of productive immune responses to allow rational prediction of vaccine efficacy. Mouse models of peripheral and mucosal bacterial and viral infections are being used to analyze T cell immune responses. Our interests lie not only with understanding immune response initiation in lymphoid tissues but also strive to comprehend the development and function of T cell responses in non-lymphoid tissues, which contain a large proportion of the responding effector and memory T cells.
Pathogens under study include Listeria monocytogenes, vesicular stomatitis virus and influenza virus. Immune responses are analyzed by flow cytometry, functional assays and genetic techniques, and confocal microscopy is being used to visualize the anatomical characteristics of immune responses in situ. For several years, our lab has also been interested in the control of immune responses by cytokines, particularly members of the gC family, including IL-2, IL-7 and IL-15. IL-15 is critical for the survival of memory CD8 T cells but the specifics of IL-15 production and acquisition in vivo are largely unknown. We have not only developed potential therapeutics based on IL-15, but we have also generated transgenic mice in which IL-15 production is indicated by a fluorescent reporter. The IL-15 system is complex and little is known regarding the control of cytokine production in vivo so this system will provide an important tool to study IL-15 biology. Our lab is also involved in the generation of novel transgenic systems for the study of immune responses not only to infections but to self antigens. In particular, we have developed transgenic mice in which model neo-self antigens can be turned on and off on demand. These models will be invaluable for understanding how endogenous T cells cope with tissue specific and developmentally regulated autoantigens. In one system, antigens are being expressed in the intestinal epithelium which allow the study of induction of tolerance versus autoimmunity in the mucosa. Overall, my research is aimed toward the use of in vivo model systems with the goal of understanding the requirements for induction and regulation of anti-microbial as well as autoreactive immune responses.
Turner, M.J. and Lefranšois, L. 2008. Limiting avidity maturation of self-specific memory CD8 T cells prevents autoimmunity. J. Exp. Med. 205:1859-1868.
Obar, J.J., Khanna, K.M. and Lefranšois, L. 2008. Endogenous na´ve CD8 T cell precursor frequency regulates primary and memory responses to infection. Immunity. 28:859-869.
Khanna, K.M., McNamara, J.T. and Lefranšois, L. 2007. Discrete anatomical stages of the endogenous CD8 T cell response to infection revealed by in situ imaging. Science. 318:116-120.
Blair, D. and Lefranšois, L. 2007. Increased competition for antigen during priming negatively impacts the generation of memory CD4 T cells. Proc. Natl. Acad. Sci. USA. 104: 15045-15050.
Turner, D.L., Cauley, L.S., Khanna, K.M. and Lefranšois, L. 2007. Persistent antigen presentation following acute vesicular stomatitis virus infection. J. Virol. 81:2039-46.
Stoklasek, T. Schluns, K.S. and Lefranšois, L. 2006. Combined IL-15/IL-15Ra immunotherapy maximizes IL-15 activity in vivo. J. Immunol. 177:6072-6080.
Zammit, D.J., Turner, D.L., Klonowski, K.D., Lefranšois, L. and Cauley, L.S. 2006. Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration. Immunity. 24:439-449.
Marzo, A.M., Klonowski, K.D., Le Bon, A., Borrow, P., Tough, D.F. and Lefranšois, L. 2005. Initial precursor frequency dictates memory CD8 T cell lineage commitment. Nature Immunol. 6:793-799.
Zammit, D.J., Cauley, L.S., Pham, Q-M. and Lefranšois, L. 2005. Dendritic cells maximize the memory CD8 T cell response to infection. Immunity. 22:561-570.
Klonowski, K. D., Williams, K.J., Marzo, A.M., Lingenheld, E.G. and Lefranšois, L. 2004. Dynamics of blood-borne CD8 memory T cell migration in vivo. Immunity. 20:551-562.
Schluns, K.S., Cabrera-Hernandez, A., Nowak, E.C., Puddington, L., Lefranšois, and Aguila, H.L. 2004. Distinct cell types control lymphoid subset development via IL-15 and IL-15Ra expression. Proc. Natl. Acad. Sci. 101:5616-5621.
Masopust, D., Vezys, V., Marzo, A. and Lefranšois, L. 2001. Preferential localization of effector memory cells in nonlymphoid tissue. Science. 291:2413-2417.
View more publications, see Pubmed listing.