Impact of ligand affinity on CD8 recent thymic emigrant responses to bacterial infection

Abstract

To explore the relative T cell receptor (TCR) sensitivity of recent thymic emigrants (RTEs) compared to mature naïve T cells, we triggered T cells with altered peptide ligands (APLs) that vary in their affinity for the TCR. Upon peptide stimulation in vitro, RTEs exhibited increased TCR signal transduction, and following infection in vivo with APL-expressing bacteria, CD8 RTEs expanded to a greater extent in response to low affinity antigens than their mature T cell counterparts. RTEs skewed to short-lived effector cells in response to all APLs but were also characterized by diminished cytokine production. RTEs responding to infection expressed increased levels of VLA-4, with consequent improved entry into inflamed tissue and pathogen clearance. These positive outcomes were offset by the enhanced capacity of RTEs to elicit autoimmunity. While RTEs exhibited increased effector responses, their memory formation differed from that of mature-derived memory T cells, with a lower proportion of central memory T cells and less efficient homing to the bone marrow. Overall, salient features of CD8 RTE biology should inform strategies to improve neonatal vaccination and therapies for cancer and HIV, as RTEs make up a large proportion of the T cells in the newborn and other lymphodepleted environments.