Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA

Nat Commun. 2017 Nov 13;8(1):1473. doi: 10.1038/s41467-017-01728-5.

Abstract

The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two major subsets based on the expression of the adhesion G protein-coupled receptor GPR56, and GPR56+ TEMRA cells display a transcriptional and proteomic program with cytotoxic features that is distinct from effector memory T cells. Moreover, GPR56+ TEMRA cells have higher levels of clonal expansion and contain the majority of virus-specific TEMRA cells. Overall, this study reveals the heterogeneity of CD4 TEMRA cells and provides insights into T-cell responses against DENV and other viral pathogens.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / classification
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Core Binding Factor Alpha 3 Subunit / biosynthesis
  • Cytomegalovirus / immunology*
  • Dengue Virus / immunology*
  • Gene Expression Profiling
  • Granzymes / biosynthesis
  • Herpesvirus 4, Human / immunology*
  • Heterogeneous-Nuclear Ribonucleoproteins / biosynthesis
  • Humans
  • Immunologic Memory / immunology
  • Leukocyte Common Antigens / metabolism*
  • Male
  • Middle Aged
  • Perforin / biosynthesis
  • Receptors, CCR7 / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Signaling Lymphocytic Activation Molecule Family / biosynthesis
  • T-Box Domain Proteins / biosynthesis
  • Young Adult

Substances

  • ADGRG1 protein, human
  • CD244 protein, human
  • Core Binding Factor Alpha 3 Subunit
  • HNRNPLL protein, human
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Receptors, CCR7
  • Receptors, G-Protein-Coupled
  • Runx3 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Perforin
  • Leukocyte Common Antigens
  • Granzymes