Phenotypic and Functional Plasticity of Gamma–Delta (γδ) T Cells in Inflammation and Tolerance

Abstract

Gamma–delta T cells (γδ T cells) are an unique group of lymphocytes and play an important role in bridging the gap between innate and adaptive immune systems under homeostatic condition as well as during infection and inflammation. They are predominantly localized into the mucosal and epithelial sites, but also exist in other peripheral tissues and secondary lymphoid organs. γδ T cells can produce cytokines and chemokines to regulate the migration of other immune cells, can bring about lysis of infected or stressed cells by secreting granzymes, provide help to B cells and induce IgE production, can present antigen to conventional T cells, activate antigen presenting cells (APC) maturation, and are also known to produce growth factors that regulate the stromal cell function. γδ T cells spontaneously produce IFN-γ and IL-17 cytokines compared to delayed differentiation of Th1 and Th17 cells. In this review, we discussed the current knowledge about the mechanism of γδ T cell function including its mode of antigen recognition, and differentiation into various subsets of γδ T cells. We also explored how γδ T cells interact with different types of innate and adaptive immune cells, and how these interactions shape the immune response highlighting the plasticity and role of these cells—protective or pathogenic under inflammatory and tolerogenic conditions.

Keywords:

• autoimmunity
• gamma–delta T cells
• regulatory CD4 T cells
• Th17 cells
• tolerance

ABBREVIATIONS
AHR	=	airway hyperresponsiveness
AhR	=	aryl hydrocarbon receptor
APC	=	antigen-presenting cells
CDR	=	complementarity-determining region
γ δ T cells	=	gamma–delta T cells
DC	=	dendritic cells
DETC	=	dendritic epidermal T cells
MHC	=	major histocompatibility complex
NK cells	=	natural killer cells
NKR	=	natural killer receptor
TCR	=	T cell receptor
TLR	=	Toll-like receptor
Tregs	=	Regulatory CD4 T cells