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