Inhibitory signaling sustains a distinct early memory CD8+ T cell precursor that is resistant to DNA damage. Academic Article uri icon

Overview

abstract

  • The developmental origins of memory T cells remain incompletely understood. During the expansion phase of acute viral infection, we identified a distinct subset of virus-specific CD8+ T cells that possessed distinct characteristics including expression of CD62L, T cell factor 1 (TCF-1), and Eomesodermin; relative quiescence; expression of activation markers; and features of limited effector differentiation. These cells were a quantitatively minor subpopulation of the TCF-1+ pool and exhibited self-renewal, heightened DNA damage surveillance activity, and preferential long-term recall capacity. Despite features of memory and somewhat restrained proliferation during the expansion phase, this subset displayed evidence of stronger TCR signaling than other responding CD8+ T cells, coupled with elevated expression of multiple inhibitory receptors including programmed cell death 1 (PD-1), lymphocyte activating gene 3 (LAG-3), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD5, and CD160. Genetic ablation of PD-1 and LAG-3 compromised the formation of this CD62Lhi TCF-1+ subset and subsequent CD8+ T cell memory. Although central memory phenotype CD8+ T cells were formed in the absence of these cells, subsequent memory CD8+ T cell recall responses were compromised. Together, these results identify an important link between genome integrity maintenance and CD8+ T cell memory. Moreover, the data indicate a role for inhibitory receptors in preserving key memory CD8+ T cell precursors during initial activation and differentiation. Identification of this rare subpopulation within the memory CD8+ T cell precursor pool may help reconcile models of the developmental origin of long-term CD8+ T cell memory.

authors

publication date

  • January 15, 2021

Research

keywords

  • CD8-Positive T-Lymphocytes
  • Listeriosis
  • Lymphocytic Choriomeningitis
  • Memory T Cells
  • Precursor Cells, T-Lymphoid

Identity

PubMed Central ID

  • PMC8258400

Scopus Document Identifier

  • 85100124882

Digital Object Identifier (DOI)

  • 10.1126/sciimmunol.abe3702

PubMed ID

  • 33452106

Additional Document Info

volume

  • 6

issue

  • 55