Lay Summary

Proposal No.   IBD-0025
Principal Investigator:  Luk Van Parijs, Ph.D.
Applicant Organization:  Massachusetts Institute of Technology (Cambridge, U.S.A.)
Project Title:  Control of regulatory T cell activity and inflammatory bowel disease by interleukin-2
Period of Award:  October 1, 2002 - September 30, 2003

T cells protect against microbes.  However, under certain conditions, these cells initiate responses that are not aimed at harmful infections, but target innocuous organisms or tissues in the body, resulting in immune-mediated tissue damage.  It is thought that T cells cause inflammatory bowel disease when they start to respond to harmless normal enteric bacteria.  An important question is why are these pathogenic T cell responses initiated and what keeps them in check in persons without inflammatory bowel disease (IBD).

A specialized population of T cells, called regulatory T cells, has been identified that functions to block the type of T cell responses that result in IBD.  At the present time, little is known about how these cells develop and how they function.  We have shown that the T cell growth factor, IL-2, is necessary for regulatory T cells to survive and prevent IBD.  Mice that lack this growth factor have very few regulatory T cells and are predisposed to developing IBD.  We now propose to study why regulatory T cells require IL-2 and how this growth factor helps prevent IBD.  We will accomplish this by studying whether regulatory T cells that lack important molecules activated by IL-2 can block IBD in a mouse model of this disease.  We will investigate how these molecules promote the function of regulatory T cells and we will also search for new molecules that are expressed in these cells only when IL-2 is present.  Our studies should provide important information on how regulatory T cells work and how they prevent IBD.  They may also provide a basis for understanding how this disease develops in humans.  It may be possible to use the information that we gain about IL-2 to develop new therapies aimed at controlling or eliminating IBD.