Dissection of the Human T-Cell Receptor γ Gene Repertoire in the Brain and Peripheral Blood Identifies Age- and Alzheimer's Disease-Associated Clonotype Profiles

Front Immunol. 2020 Jan 29:11:12. doi: 10.3389/fimmu.2020.00012. eCollection 2020.

Abstract

The immune system contributes to neurodegenerative pathologies. However, the roles of γδ T cells in Alzheimer's disease (AD) are poorly understood. Here, we evaluated somatic variability of T-cell receptor γ genes (TRGs) in patients with AD. We performed deep sequencing of the CDR3 region of TRGs in patients with AD and control patients without dementia. TRG clones were clearly detectable in peripheral blood (PB) and non-neuronal cell populations in human brains. TRG repertoire diversity was reduced during aging. Compared with the PB, the brain showed reduced TRGV9 clonotypes but was enriched in TRGV2/4/8 clonotypes. AD-associated TRG profiles were found in both the PB and brain. Moreover, some groups of clonotypes were more specific for the brain or blood in patients with AD compared to those in controls. Our pilot deep analysis of T-cell receptor diversities in AD revealed putative brain and AD-associated immunogenic markers.

Keywords: Alzheimer's disease; T-cell receptor γ genes; clonotype; immune repertoire; immunogenic marker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Aging / immunology*
  • Alzheimer Disease / blood*
  • Alzheimer Disease / immunology*
  • Brain / immunology*
  • Clone Cells / immunology*
  • Complementarity Determining Regions / genetics
  • Female
  • Genes, T-Cell Receptor gamma*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Receptors, Antigen, T-Cell, gamma-delta / blood
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Young Adult

Substances

  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell, gamma-delta