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Leo Lefrançois

Professor of Immunology
Immunology Department Chairman
Director, Center for Integrated Immunology and Vaccine Research
Director, Flow Cytometry Facility
Lefrançois@nso1.uchc.edu
Lefrançois Lab Page

Dr. Leo Lefrancois
Areas of Interest

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 C 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.

Lab Rotation Projects

1. Analysis of requirements for memory T cell lineage development in response to viral and bacterial infections.

2. Imaging of memory T cell localization in situ using confocal microscopy.

3. Assessing the role of CD4 T cell help in generation and maintenance of CD8 T cell memory.

Publications

Selected Publications

Turner, M.J. and Lefrançois, 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 Lefrançois, L. 2008. Endogenous naïve CD8 T cell precursor frequency regulates primary and memory responses to infection. Immunity 28:859-869.

Khanna, K.M., McNamara, J.T. and Lefrançois, 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 Lefrançois, 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 Lefrançois, L. 2007. Persistent antigen presentation following acute vesicular stomatitis virus infection. J. Virol, 81:2039-46.

Stoklasek, T. Schluns, K.S. and Lefrançois, L. 2006. Combined IL-15/IL-15R immunotherapy maximizes IL-15 activity in vivo. J. Immunol., 177:6072-6080.

Zammit, D.J., Turner, D.L., Klonowski, K.D., Lefrançois, 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 Lefrançois, L. 2005. Initial precursor frequency dictates memory CD8 T cell lineage commitment. Nature Immunol. 6:793-799.

Paper icon View more publications, see Pubmed listing.

rev. 2/09

  
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