The function of γδ T cells in innate immunity (original) (raw)

γδ T Lymphocytes—Selectable Cells Within the Innate System?

Journal of Clinical Immunology, 2007

Lymphocytes expressing γ δ T cell receptors (TCR) constitute an entire system of functionally specialized subsets that have been implicated in the regulation of immune responses, including responses to pathogens and allergens, and in tissue repair. The γ δ TCRs share structural features with adaptive receptors and peripheral selection of γ δ T cells occurs. Nevertheless, their specificities may be primarily directed at self-determinants, and the responses of γ δ T cells exhibit innate characteristics. Continuous cross talk between γ δ T cells and myeloid cells is evident in histological studies and in in vitro co-culture experiments, suggesting that γ δ T cells play a functional role as an integral component of the innate immune system.

Six-of-the-best: unique contributions of γδ T cells to immunology

Nature Reviews Immunology, 2013

Preface γδ T cells are a unique and conserved population of lymphocytes that have been the subject of a recent explosion of interest owing to their essential contributions to many types of immune response and immunopathology. But what does the integration of recent and longestablished studies really tell us about these cells and their place in immunology? The time is ripe to consider where strong evidence exists for their unique and critical functions. We conclude that whereas αβ T cells and B cells are commonly viewed as contributing primarily to antigen-specific effector and memory phases of immunity, γδ T cells are distinct in that they combine conventional adaptive potentials, inherent in their T cell receptors (TCRs) and pleiotropic effector functions, with rapid, innate-like responses that place them in the initiation phase of immune reactions. This underpins a revised perspective on lymphocyte biology and the regulation of immunogenicity.

Gammadelta T cells: innately adaptive immune cells?

International Reviews of Immunology, 2013

T cells employ a cell surface heterodimeric molecule, the T cell receptor (TCR), to recognize specific antigens (Ags) presented by major histocompatibility complex (MHC) molecules and carry out adaptive immune responses. Most T cells possess a TCR with an α and a β chain. However, a TCR constituted by a γ and a δ chain has been described, defining a novel subset of T cells. γδ TCRs specific for a wide variety of ligands, including bacterial phosphoantigens, nonclassical MHC-I molecules and unprocessed proteins, have been found, greatly expanding the horizons of T cell immune recognition. This review aims to provide background in γδ T cell history and function in mouse and man, as well as to provide a critical view of some of the latest developments on this still enigmatic class of immune cells.

Innate and adaptive γδ T cells: How, when, and why

Immunological Reviews, 2020

Summaryγδ T cells comprise the third cell lineage of lymphocytes that use, like αβ T cells and B cells, V(D)J gene rearrangement with the potential to generate a highly diverse T cell receptor (TCR) repertoire. There is no obvious conservation of γδ T cell subsets (based on TCR repertoire and/or function) between mice and human, leading to the notion that human and mouse γδ T cells are highly different. In this review, we focus on human γδ T cells, building on recent studies using high‐throughput sequencing to analyze the TCR repertoire in various settings. We make then the comparison with mouse γδ T cell subsets highlighting the similarities and differences and describe the remarkable changes during lifespan of innate and adaptive γδ T cells. Finally, we propose mechanisms contributing to the generation of innate versus adaptive γδ T cells. We conclude that key elements related to the generation of the γδ TCR repertoire and γδ T cell activation/development are conserved between hum...

γδ T cell development — having the strength to get there

Current Opinion in Immunology, 2005

gd T cells play critical roles in immune regulation, tumour surveillance and specific primary immune responses. Mature gd cells derive from thymic precursors that also generate ab T cells. Recent reports have highlighted the impact of the strength of signal received via the T cell receptor on T cell lineage commitment, and the importance of cross-talk between committed ab thymocytes and bipotential progenitors for normal gd T cell differentiation. Studies on T cell receptormediated selection of gd cells have supported the view that these unconventional T cells are positively rather than negatively selected on cognate self antigen.

γδ T cell effector functions: a blend of innate programming and acquired plasticity

Nature Reviews Immunology, 2010

The integrity of higher vertebrates is maintained through protective mechanisms that can detect stress-induced determinants that arise following infection, injury or cellular alterations. This surveillance involves both innate and adaptive immune processes. Innate responses, mainly mediated by natural killer (NK) cells and myelomonocytic cells, are readily activated following engagement of non-clonal receptors referred to as pattern recognition receptors (PRRs), which are specific for determinants that are broadly expressed by microorganisms or are upregulated by host cells in response to cell stress 1,2. PRR engagement triggers an inflammatory response that initially leads to increased microbicidal and cytotoxic functions of immune cells, and clearance of the eliciting agent, and later to tissue repair and immune downmodulation 3. Adaptive immune cells have overall functions that are similar to those of innate cells but, owing to immuno logical memory, they can yield stronger and faster responses after repeated exposure to a given eliciting agent 4. The establishment of immunological memory implies expansion of T and B cells, specific for the eliciting antigen, after engagement of clonally distributed T cell receptors (TCRs) and B cell receptors (BCRs). Clonally expanded T and B cell populations acquire a restricted set of effector functions that are presumably best suited for clearance of the eliciting agent at a given time point in a given tissue. Innate cells are involved in the induction of adaptive immune responses of appropriate strength, kinetics and function in two ways. First, they efficiently internalize pathogens and dying cells and process them into peptide antigens that are presented in the context of MHC molecules to conventional αβ T cells. Second, they integrate danger and inflammatory cues and translate them into stimuli that lead to proper functional polarization of αβ T cell and B cell responses 4. Although, generally, innate immune responses precede adaptive immune responses, a reverse interplay from adaptive to innate immune effectors also contributes to the early recruitment and activation of innate immune cells and subsequent functional polarization of MHC-restricted T cells. T cells contributing to this reverse crosstalk involve subsets of αβ T cells restricted by the non-polymorphic MHC class I-like molecules CD1d and MHC-related protein 1 (MR1) (known as invariant NKT cells and mucosa-associated invariant T cells, respectively), as well as T cells expressing γδ TCRs 5,6. These lympho cytes have been termed non-conventional, innate-like or transitional T cells, owing to several distinguishing features that are shared with innate immune cells 5,7. Similar to other non-conventional T cells, γδ T cells recognize conserved non-peptide antigens that are upregulated by stressed cells, the expression modalities and distribution of which resemble those of pathogenassociated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) recognized by PRRs. These cells acquire a pre-activated phenotype associated with the upregulation of memory markers early in their development. This pre-activated status allows rapid induction of effector functions following the detection of tissue stress. Another important feature of γδ T cells is their tropism for epithelial surfaces, such as those of the liver and skin, and mucosae from respiratory, digestive and reproductive

γδ T Cells and the Lymphoid Stress-Surveillance Response

Immunity, 2009

The investigation of gd T cells has identified a rapid lymphoid stress-surveillance response to microbial and nonmicrobial tissue perturbation. In addition to providing local protection, this response provides an immediate source of cytokines, chemokines, and other functions that can substantially affect downstream, adaptive immunity. Recent studies have identified striking mechanisms by which gd cells meet the requirements of stress surveillance. For example, high response frequencies can reflect a unique nature of antigen engagement by the T cell receptor (TCR), developmental focusing of the repertoire by selection events, or the use of nonclonotypic receptors to initiate responses. Likewise, rapid functional deployment can be facilitated by the preprogramming of gd cells during development. Additionally, gd cells can directly influence adaptive immunity by functioning as antigen-presenting cells. With lymphoid stress surveillance likely to underpin numerous aspects of inflammation, tumor immunology, infectious disease, and autoimmunity, this perspective considers its properties and its emerging potential for clinical manipulation.