Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts

J Immunol. 2015 Aug 15;195(4):1449-58. doi: 10.4049/jimmunol.1500375. Epub 2015 Jun 29.


To better apprehend γ/δ T cell biological functions in the periphery, it appears crucial to identify markers highlighting the existence of distinct phenotypic and functional γ/δ T cell subsets. Interestingly, the expression of CD44 and Ly-6C subdivides murine peripheral γ/δ T cells into several subsets, with Ly-6C(-) CD44(hi) γ/δ T cells corresponding to the IL-17-producing CD27(-) γ/δ T cell subset exhibiting innate-like features. By comparing the other subsets to naive and memory CD8(+) α/β T cells, in this study, we show that Ly-6C(- or +) CD44(lo) and Ly-6C(+)CD44(hi) γ/δ T cells greatly resemble, and behave like, their CD8(+) α/β T cell counterparts. First, like memory CD8(+) α/β T cells, Ly-6C(+)CD44(hi) γ/δ T cells are sparse in the thymus but largely increased in proportion in tissues. Second, similarly to naive CD8 α/β T cells, CD44(lo) γ/δ T cells are poorly cycling in vivo in the steady state, and their proportion declines with age in secondary lymphoid organs. Third, CD44(lo) γ/δ T cells undergo spontaneous proliferation and convert to a memory-like Ly-6C(+)CD44(hi) phenotype in response to lymphopenia. Finally, CD44(lo) γ/δ T cells have an intrinsic high plasticity as, upon appropriate stimulation, they are capable of differentiating nonetheless into Th17-like and Th1-like cells but also into fully functional Foxp3(+) induced regulatory T cell-like γ/δ T cells. Thus, peripheral CD27(+) γ/δ T cells, commonly considered as a functionally related T cell compartment, actually share many common features with adaptive α/β T cells, as both lineages include naive-like and memory-like lymphocytes with distinct phenotypic, functional, and homeostatic characteristics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Antigens, Ly / genetics
  • Antigens, Ly / metabolism
  • Gene Expression
  • Homeostasis
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Immunophenotyping
  • Interleukin-17 / biosynthesis
  • Lymphopenia / immunology
  • Lymphopenia / metabolism
  • Mice
  • Mice, Knockout
  • Phenotype
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7


  • Antigens, Ly
  • Hyaluronan Receptors
  • Interleukin-17
  • Ly-6C antigen, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tumor Necrosis Factor Receptor Superfamily, Member 7