Presenting Author: Colin J Raposo
, Graduate Student at Stanford Univ. Sch. of Med., Gladstone Insts.
Abstract:
Chronic stimulation of CD8+ T cells leads them to enter a state of restrained functionality known as exhaustion. Removal of chronic stimulation leads exhausted T cells to take on a memory phenotype that retains an epigenetic imprint of previous chronic stimulation. However, the fate of individual exhausted T cell clones upon antigen removal remains unclear. Our group has recently shown that CD8+ T cell responses to chronic infection are comprised of many T cell clones with unique T cell receptors that each take on unique distributions of fates. To study the impact of antigen clearance on individual exhausted T cell clones, we analyzed T cell repertoires of mice infected with chronic lymphocytic choriomeningitis virus (LCMV) during infection and after peripheral viral clearance. We show that individual LCMV-specific clones have differential capacity to persist past viral clearance and take on clonally and phenotypically distinct cell states. These states include exhausted phenotypes and central memory-like cells that are characterized by minimal epigenetic imprinting of chronic stimulation. Furthermore, chronic memory cells have altered ability to differentiate upon rechallenge, which enables their preferential survival compared to acute memory cells when rechallenged with chronic LCMV. Together, these data illustrate that a subset of clones within the exhausted T cell pool is primed to form memory and protect the host from a secondary infection.
A clonally restricted subset of exhausted CD8+ T cells maintains the capacity to form memory
Category
Poster and Podium (Block Symposium)
Description
Custom CSS
double-click to edit, do not edit in source
Date: May 4 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1