Environmental Cues Dictate the Fate of Individual CD8+ T Cells Responding to Infection

Abstract

Summary Many studies have examined pathways controlling effector T cell differentiation, but less is known about the fate of individual CD8+ T cells during infection. Here, we examined the antiviral and anti-bacterial responses of single CD8+ T cells from the polyclonal repertoire. The progeny of naïve clonal CD8+ T cells displayed unique profiles of differentiation based on extrinsic pathogen-induced environmental cues, with some clones demonstrating extreme bias towards a single developmental pathway. Moreover, even within the same animal, a single naïve CD8++ T cell exhibited distinct fates that were controlled by tissue-specific events. However, memory CD8+ T cells relied on intrinsic factors to control differentiation upon challenge. Our results demonstrate that stochastic and instructive events differentially contribute to shaping the primary and secondary CD8+ T cell response. and provide insight into the underlying forces that drive effector differentiation and protective memory formation.

Clonal Evolution of CD8+T Cell Responses against Latent Viruses: Relationship among Phenotype, Localization, and Function

“…However, it has been shown that one clone can give rise to both acute-phase short-lived effector cells and memory precursor cells (46) and that this balance is altered by the kind of infection, route of infection, tissue-specific events, and other factors (46)(47)(48). Price et al (44) showed that during latency, EBV-and hCMV-specific CD8 ϩ T cells with low-affinity TCRs have a memory-type phenotype, whereas the high-affinity TCR-expressing cells have an effector-type phenotype.…”

Proteasome activity regulates CD8+ T lymphocyte metabolism and fate specification

“…Prior studies have shown that a single naive CD8 + T cell can give rise to both terminal effector and memory lymphocytes (5)(6)(7). One mechanism by which terminal effector and memory cells can be derived from a single naive cell is asymmetric cell division, an evolutionarily conserved process in which cellular components are unequally localized to opposing poles of a mitotic cell, thereby resulting in daughter cells with tendencies toward distinct fates from their inception (8,9).…”

Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation

“…[6][7][8][9][10] In humans, however, this pursuit has been limited by ethical and technical constraints. Hematopoietic stem cell transplantation (HSCT) provides a unique setting to longitudinally study the dynamics of discrete T-cell populations upon transfer directly in humans.…”