Gamma delta T cell
Gamma delta T cells (γδ T cells) are
The antigenic molecules that activate γδ T cells are largely unknown. γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes, although some recognize MHC class Ib molecules. γδ T cells are believed to have a prominent role in lipid antigen recognition. They are of an invariant nature. They may be triggered by alarm signals such as heat shock proteins (HSP).
A γδ-T-cell sub-population exists within the
Innate and adaptive immunity
The conditions that lead to responses of γδ T cells are not fully understood, and current concepts of them as 'first line of defense', 'regulatory cells', or 'bridge between innate and adaptive responses'
Like other 'unconventional' T cell subsets bearing invariant TCRs, such as
γδ T cells may be considered a component of adaptive immunity in that they rearrange TCR genes to produce junctional diversity and can develop a memory phenotype. However, the various subsets may also be considered part of the innate immunity[4] in which a specific TCR can function as a pattern recognition receptor.[5] For example, according to this paradigm, large numbers of (human) Vγ9/Vδ2 T cells respond within hours to common molecules produced by microbes, and highly restricted intraepithelial Vδ1 T cells will respond to stressed epithelial cells bearing sentinels of danger.
Recent work has shown that human Vγ9/Vδ2 T cells are also capable of phagocytosis, a function previously exclusive to innate myeloid lineage cells such as neutrophils, monocytes and dendritic cells [6] This provides further evidence that the biology of γδ T cells spans both innate and adaptive immune responses.
Murine thermogenesis
Recently, it was believed that γδ17 T cells were only able to produce IL-17 in acute infections. It was recently discovered that γδ17 T cells can produce IL-17 even when the immune response is not induced. These cells are likely to be generated from fetal γδ thymocytes and as they egress from the thymus, they will progress to non-lymphoid tissues such as lungs, peritoneal cavity, dermis, tongue and uterus.[7]
The γδ17 T that will accumulate in the adipose tissue (dermis) will not only controls the homeostasis of regulatory T cells but also an adaptive thermogenesis, therefore they are able to control the maintenance of core body temperature.[8] Using aging mice as a model, the molecular and cellular mechanisms that act under thermoneutrality circumstances (steady state) or after cold exposure has been recently acknowledged,
When the mice is on a
Autoimmunity
γδ T cells have clinical association with many autoimmune diseases.
Inflammatory bowel diseases IBD
γδ T cells are a major T cell subset of intraepithelial lymphocytes (IEL) present in the epithelial layer of
is responsible for cell-mediated production of antimicrobial peptides and tissue repair.On the other hand, pathogenic γδ T cells produce
Type 1 diabetes T1D
Rheumatoid arthritis RA
RA is a chronic autoimmune disease caused by accumulation of self-reactive T cells, which are induced by inflammation in
Multiple sclerosis MS
γδ T cells are involved in development of this autoimmune disease. They are
Psoriasis
Psoriasis is one of the autoimmune diseases in which the γδ T cells together with
Cancer
Non-MHC restricted recognition of
γδ T cells can be divided into effector and regulatory cells:
Effector functions
After infiltrating a tumor as a response to
Regulatory functions
γδ T cells perform a regulatory and suppressive role in the TME expression of
Gene families in different species
Laboratory mice (Mus musculus)
Mouse Vγ chains
This table summarizes the nomenclature of mouse Vγ chains and indicates monoclonal antibodies often used to identify these chains. This system has been best described in strain C57BL/6 and might not apply well to other strains. There are two systems of nomenclature in use (Heilig; Garman), and many writers do not indicate which system they use. For example, the IMGT (International Immunogenetics Information System) uses the Heilig notation, but does not indicate this fact on its website.[citation needed] This table refers to variable chain Vγ gene segments and to monoclonal antibodies that detect the corresponding Vγ protein chains. Note that Adrian Hayday's proposed nomenclature is not widely used,[citation needed] leaving considerable confusion in the literature. One advantage and weakness of the Hayday nomenclature is that it is based on the gene order in the B6 genome, but this might not apply to other strains.
Heilig and Tonegawa's system[22] |
Garman's system [23] |
"Hayday's system[24]" | antibodies | comments |
---|---|---|---|---|
Vγ5 | Vγ3 | GV1S1 | 536; 17D1 specific for Vγ5(Heilig)+Vδ1 clonotype | Skin, Jγ1Cγ1 |
Vγ6 | Vγ4 | GV2S1 | 17D1; can detect Vγ6Vδ1 when pretreated with GL3 antibodies | reproductive mucosa;Jγ1Cγ1 |
Vγ4 | Vγ2 | GV3S1 | UC310A6 | lung;Jγ1Cγ1 |
Vγ7 | Vγ5 | GV4S1 | F2.67 Pereira | most common form in intestinal IEL orthologous to human Vγ1 Jγ1Cγ1 |
Vγ1 | Vγ1.1 | GV5S1 | 2.11 Pereira 1995 | peripheral lymphoid tissues;Jγ4Cγ4 |
Vγ2 | Vγ1.2 | GV5S2 | Jγ1Cγ1 | |
Vγ3 | Vγ1.3 | GV5S3 | Jγ3-pseudoCγ3 |
Human forms
Human Vδ2+ T cells
Vγ9/Vδ2 T cells are unique to humans and primates and represent a minor and unconventional constituent of the leukocyte population in peripheral blood (0.5-5%), yet they are assumed to play an early and essential role in sensing 'danger' by invading pathogens as they expand dramatically in many acute infections and may exceed all other lymphocytes within a few days, e.g. in tuberculosis, salmonellosis, ehrlichiosis, brucellosis, tularemia, listeriosis, toxoplasmosis, and malaria.
Of note, all Vγ9/Vδ2 T cells recognize the same small microbial compound (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (
It is still not clear whether these
These Vγ9Vδ2 T cells can also behave like professional antigen-presenting cells (
Human non-Vδ2+ T cells
The extensive structural diversity of Vδ1 and Vδ3 TCRs and the existence of Vδ1+ clones reactive against MHC, MHC-like, or non-MHC molecules suggest recognition of a highly diverse and heterogeneous set of antigens by non-Vδ2 cells, although cognate interactions between non-Vδ2 TCRs and any of these antigens have not been shown yet. MHC class-I-chain-related gene A (MICA) has also been proposed as an important tumor antigen recognized by Vδ1+ T cells. However, the very low affinity of MICA–Vδ1 TCR interactions estimated by surface plasmon resonance analyses raises doubts about the functional relevance of MICA or MHC class-I-chain-related gene B (MICB) recognition by Vδ1+ TCRs.
Non-Vδ2 γδ T cells are expanded in various infectious contexts involving intracellular bacteria (
A recent study has identified a specific subset of
The major outcome of this study is the clinical relevance of this cells, which can be used a prognostic marker in the colorectal cancer (CRC), in order to follow-up its progression. Lower frequencies of NKp46+/Vδ1 IELs in healthy intestinal tissues surrounding the tumor mass, associate with a higher tumor progression and metastasis. It is acknowledged that this subset can control the metastasis, so the higher levels of this population, the less probabilities for the tumor to progress and proliferate to other tissues.[30]
See also
- Naive T cells
- Memory T cells
- Helper T cells
- Cytotoxic T cells
- Natural killer T cells
- Innate immune system
- Adaptive immune system
- Regulatory T cells
References
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Further reading
- PMID 10837080.
- Girardi M (January 2006). "Immunosurveillance and immunoregulation by gammadelta T cells". The Journal of Investigative Dermatology. 126 (1): 25–31. PMID 16417214.
- Thedrez A, Sabourin C, Gertner J, Devilder MC, Allain-Maillet S, Fournié JJ, et al. (February 2007). "Self/non-self discrimination by human gammadelta T cells: simple solutions for a complex issue?". Immunological Reviews. 215 (1): 123–135. S2CID 86017229.
- Dolgin, Elie (2022-06-01). "Unconventional γδ T cells 'the new black' in cancer therapy". Nature Biotechnology. 40 (6): 805–808. S2CID 249709518.