Leo Lefrançois

Center for Integrated Immunology and Vaccine Research, Department. of Immunology, University of Connecticut Health Center, Farmington, CT, USA

Title: Dynamics of peripheral CD8 T cell tolerance induction

Abstract:

Many studies have examined the induction of T cell tolerance using a variety of systems. In some cases, tolerance driven by antigen expression in the thymus results in central tolerance thereby obviating the need for peripheral tolerance. Even in the case of presumed tissue-specific protein expression, the activity of Aire may result in central tolerance induction during thymocyte maturation.  In some cases, low-affinity self-specific T cell clones escape central tolerance and when challenged, may mount immune responses in the periphery that either provide protection against infection or cause autoimmunity. Other work using various transgenic systems has more directly examined peripheral tolerance, primarily using adoptive transfer of TCR transgenic T cells, with some notable exceptions. Nevertheless, the mechanisms by which peripheral tolerance is induced and maintained for primary and memory endogenous CD8 T cells have not been fully elucidated. We have developed an inducible and reversible transgenic system in which neo-antigen expression can be effectively regulated at will. This system has now been utilized to study the response of endogenous naive and memory CD8 T cells to induced peripheral self-antigen.  The salient features of the response will be discussed with respect to mechanisms of CD8 T cell tolerance induction.

Biography:

Dr. Lefrançois received his Ph.D. in Immunology from Wake Forest University in 1982. His postdoctoral research was performed in the laboratory of Dr. Michael Bevan at Scripps Clinic and Research Foundation, where he developed an interest in CD8 T cell biology and mucosal immunology. In 1986, Dr. Lefrançois joined the Department of Cell Biology at The Upjohn Company in Kalamazoo, MI where he continued his work on T cell immunology. In 1991, Dr. Lefrançois joined the Immunology faculty of the University of Connecticut Health Center where he currently studies the T cell immune response to infection and to self-antigens.