A T cell receptor transgenic model for studying CD4+ effector and regulatory T cells in bacterial-induced colitis. (360G-Wellcome-081056_Z_06_Z)

The intestinal bacterial flora and the CD4+ T cell response to these bacteria play an important role in the induction and regulation of chronic intestinal inflammation. The process by which bacteria-specific CD4+ T cell responses are initiated, and the factors that determine pathogenic versus disease-protective CD4+ T cell effector choice, are however not well understood. The objectives of this project are to define the mechanisms by which specific bacterial antigen/CD4+ T cell interactions trig ger colitis in disease-susceptible hosts and suppress its induction in disease-resistant hosts. We will use a newly developed transgenic mouse model based on the T cell receptor of a disease-inducing CD4+ T cell clone specific for the flagellar hook protein (FHP) of Helicobacter hepaticus. This system will enable us to distinguish bacterial from host-directed immune responses and to study the development of pathogenic effector and disease-protective T regulatory (Treg) cells. The goals of the pr oject are to i) identify the process whereby FHP-specific CD4+ T cells trigger inflammation in the intestine of H. hepaticus-infected mice, ii) define the interaction between H. hepaticus and dendritic cells (DCs), and iii) determine whether mucosal DCs can induce the differentiation of FHP-specific CD4+ Treg cells.