Human γδ T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection

Nat Immunol. 2017 Apr;18(4):393-401. doi: 10.1038/ni.3686. Epub 2017 Feb 20.

Abstract

To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding γδ TCRs (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires were private. In patients undergoing HSC transplantation, γδ T cells were quickly reconstituted; however, they had profoundly altered TCR repertoires. Notably, the clonal proliferation of individual virus-reactive γδ TCR sequences in patients with reactivation of cytomegalovirus revealed strong evidence for adaptive anti-viral γδ T cell immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clonal Evolution* / genetics
  • Clonal Evolution* / immunology
  • Cytomegalovirus Infections / genetics
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Gene Rearrangement, T-Lymphocyte
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Transplantation, Homologous

Substances

  • Receptors, Antigen, T-Cell, gamma-delta