Self/non‐self discrimination by human γδ T cells: simple solutions for a complex issue?
- 2 February 2007
- journal article
- review article
- Published by Wiley in Immunological Reviews
- Vol. 215 (1), 123-135
- https://doi.org/10.1111/j.1600-065x.2006.00468.x
Abstract
Although gammadelta T cells express clonally distributed T-cell receptors (TCRs), a hallmark of adaptive immunity, they are classically considered as innate-like effectors, owing to the high frequency of preactivated gammadelta T cells, with restricted antigen recognition repertoire in particular tissue locations. Actually, such features are shared only by a fraction of gammadelta T-cell subsets located in the skin and reproductive organ mucosa in rodents or in peripheral blood in humans. By contrast, other gammadelta subsets, e.g. those found in rodent and human spleen, show diverse antigenic reactivity patterns and mixed naive/memory phenotypes. Thus, gammadelta T cells are made of both 'primitive' subsets endowed with innate-like properties and 'evolved' subsets able to mount anamnestic responses like conventional major histocompatibility complex-restricted alphabeta T cells. In this article, we show that human gammadelta T cells, although heterogeneous, do share recurrent innate features that distinguish them from mainstream alphabeta T cells. In particular, most of them are activated on TCR- or natural killer receptor-mediated recognition of a restricted set of conserved yet poorly defined endogenous stress determinants. This rather simple recognition mechanism allows human gammadelta T cells to discriminate healthy cells from altered cells and to exert a variety of immunostimulatory or regulatory functions. The recent availability of synthetic gammadelta T-cell agonists mimicking these natural stress-induced ligands have fostered development of immunotherapeutic strategies, with broad indications against infectious and tumor diseases, which are briefly reviewed here.Keywords
This publication has 83 references indexed in Scilit:
- αβ T-Cell Receptor Engineered γδ T Cells Mediate Effective Antileukemic ReactivityCancer Research, 2006
- A variant of SCID with specific immune responses and predominance of T cellsJCI Insight, 2005
- Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patientsThe Journal of Experimental Medicine, 2005
- Effect Of Human Natural Killer and γδ T Cells on the Growth of Human Autologous Melanoma Xenografts in SCID MiceCancer Research, 2004
- The Distinct Contributions of Murine T Cell Receptor (TCR)γδ+ and TCRαβ+ T Cells to Different Stages of Chemically Induced Skin CancerThe Journal of Experimental Medicine, 2003
- γδ T cells for immune therapy of patients with lymphoid malignanciesBlood, 2003
- MICA Engagement by Human Vγ2Vδ2 T Cells Enhances Their Antigen-Dependent Effector FunctionImmunity, 2001
- γδ Cells: A Right Time and a Right Place for a Conserved Third Way of ProtectionAnnual Review of Immunology, 2000
- Inhibitory MHC class I receptors on γδ T cells in tumour immunity and autoimmunityImmunology Today, 2000
- Self-Recognition of Cd1 by γ/δ T CellsThe Journal of Experimental Medicine, 2000