CD8 T CELL ACTIVATION AND MIGRATION IN VIVO

University Of Connecticut Sch Of Med/Dnt, Farmington CT

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Abstract

The main focus of this proposal is to determine the in vivo requirements for CD8 T cell activation and migration to the intestinal mucosa. Our preliminary results indicate interesting migratory patterns following activation of TCR transgenic CD8 T cells by the soluble antigen, ovalbumin. In particular, an accumulation of activated CD8 T cells with unique phenotypes occurs in the mesenteric lymph nodes and in the lamina propria and intestinal epithelium. Our system allows for the first time an anlysis of naive intestinal T cells and visualization of a primary immune response in the intestinal mucosa. In addition we have employed an adoptive transfer system in which small numbers of TCR transgenic T cells are transferred to normal hosts. Following immunization we are then able to observe migration to mucosal tissues and modulation of adhesion/homing receptors. Our preliminary data indicates that ICAM-1 and CD18 integrins are important players in the process of intestinal T cell activation and homing. The experiments described will focus on further definition of the model system, defining the adhesion/activation molecules involved in CD8 T cell activation and migration, and producing model systems to study antigen presentation and recognition in intestinal epithelial cells. The aims of the proposal are: Aim 1: To define the parameters for activation of CD8+ T cells in an in vivo model. Aim 2: To determine the molecular interactions necessary for CD8+ T cell activation and trafficking to the intestine in vivo. Aim 3: To determine the role of antigen expressed by intestinal epithelium in T cell activation and tolerance induction. Overall, the experiments proposed will provide a comprehensive analysis of the consequences of CD8 T cell activation on the intestinal immune system.