Lefrançois Lab
The Lefrançois lab is in the Department of Immunology,
University of Connecticut School of Medicine.
Research in the Lefrançois Lab
The main focus of the Lefrançois lab research is to
understand the T cell immune response to both microbial
infections and to self-antigens. Understanding the dichotomy
between the response to self-antigens in the apparent absence of
inflammation and the response to the antigens presented in the
context of an inflammatory infection will teach us a great deal
about the rules governing the immune system. 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 to infections and also
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, our 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. |
