Tissue Adaptations of Memory and Tissue-Resident Gamma Delta T Cells

Abstract

Epithelial and mucosal barriers are critical interfaces physically separating the body from the outside environment and are the tissues most exposed to microorganisms and potential inflammatory agents. The integrity of these tissues requires fine tuning of the local immune system to enable the efficient elimination of invasive pathogens while simultaneously preserving a beneficial relationship with commensal organisms and preventing autoimmunity. Although they only represent a small fraction of circulating and lymphoid T cells, γδ T cells form a substantial population at barrier sites and even outnumber conventional αβ T cells in some tissues. After their egress from the thymus, several γδ T cell subsets naturally establish residency in predetermined mucosal and epithelial locations, as exemplified by the restricted location of murine Vγ5+ and Vγ3Vδ1+ T cell subsets to the intestinal epithelium and epidermis, respectively. Because of their preferential location in barrier sites, γδ T cells are often directly or indirectly influenced by the microbiota or the pathogens that invade these sites. More recently, a growing body of studies have shown that γδ T cells form long-lived memory populations upon local inflammation or bacterial infection, some of which permanently populate the affected tissues after pathogen clearance or resolution of inflammation. Natural and induced resident γδ T cells have been implicated in many beneficial processes such as tissue homeostasis and pathogen control, but their presence may also exacerbate local inflammation under certain circumstances. Further understanding of the biology and role of these unconventional resident T cells in homeostasis and disease may shed light on potentially novel vaccines and therapies.

The microbiome and immune memory formation

“…Gamma delta (cd) T cells are thymus-derived unconventional T cells that display innate as well as adaptive immunological features. 42 While cd T cells represent only a small fraction of T cells in the circulation or lymphoid tissues, they form a substantial tissue-resident population at epithelial and mucosal barrier sites and are therefore likely influenced by the intestinal microbiota. Some tissues contain highly restricted or specialized cd T-cell populations, such as Vc5 + T cells, that are exclusively found in the intestinal epithelium.…”

The Role of Tissue-resident γδ T Cells in Stress Surveillance and Tissue Maintenance

“…DETC and γδ IELs reside in close proximity to microorganisms in the skin and intestine, respectively, and function in the control of both host microbiota and invading bacteria [106]. While the overall impact on γδ T cell-mediated barrier maintenance is unknown, studies in germ-free and antibiotic-treated mice have suggested that the microbiota can influence the functions of γδ T cells in these tissues, and the presence of commensals is required for the normal distribution and migration of γδ IELs [106,107]. γδ IELs have been described as having an "activated but resting" phenotype in which cytotoxic genes are expressed at steady state alongside the expression of inhibitory receptors [108,109], a combination that may allow a rapid response rate while maintaining control over effector function at homeostasis.…”

The Aging of γδ T Cells

“…Mouse γδ subsets have been suggested to have an innate-like biology. However, there is evidence in multiple models which suggests that IL-17 producing Vγ6+ T cells and Vγ4+ T cells (γδ17 T cells) undergo adaptive-like differentiation through naïve precursors into mature γδ17 T cells in peripheral lymphoid organs [108]. In terms of aging, Chen et al demonstrated that aging alters TCRδ chain usage and the clonal structure of γδ T cells.…”