Gamma delta T cell

In fact, γδ T cells form an entire lymphocyte system that develops under the influence of other leukocytes in the thymus and in the periphery.

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.

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.

[8] Using aging mice as a model, the molecular and cellular mechanisms that act under thermoneutrality circumstances (steady state) or after cold exposure have recently been acknowledged.

On the other hand, it has been shown that, after exposing mice to cold, the production of TNF and IL-17 will act on the adipocytes uncoupling the protein UCP1, which is required for inducing a UCP1-dependent thermogenic program.

Matrix metalloproteinases and NO present in inflamed tissue damage and degrade basal membrane, leading to development of IBD.

[12] RA is a chronic autoimmune disease caused by accumulation of self-reactive T cells, which are induced by inflammation in synovial fluid and joints.

Matrix metalloproteinases and cathepsins induced by inflammatory cytokines, together with RANKL, cause bone and cartilage erosion, which leads to RA development.

The major outcome is that the measurement of these cells in blood and skin lesions can be used as a marker in order to follow up the psoriasis progression.

γδ T cells secrete IFN-γ and IL-17, which leads to higher expression of MHC-I, positive regulation of cytotoxic T lymphocytes and induction of anti-tumor response.

Note that Adrian Hayday's proposed nomenclature is not widely used,[citation needed] leaving considerable confusion in the literature.

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.

[25] HMB-PP is an essential metabolite in most pathogenic bacteria including Mycobacterium tuberculosis and malaria parasites, but is absent from the human host.

Of pharmacological interest and with bioactivities comparable to that of IPP are synthetic aminobisphosphonates such as zoledronate (Zometa) or pamidronate (Aredia), that are widely used to treat osteoporosis and bone metastases, and incidentally act as Vγ9/Vδ2 T cell receptor agonists.

However, increasing evidence suggests that these aminobisphosphonate 'antigens' are not recognised directly by Vγ9/Vδ2 T cells and in fact act indirectly, via their effects on the mevalonate biosynthetic pathway, leading to an accumulation of IPP.

[26] Finally, certain alkylated amines have been described to activate Vγ9/Vδ2 T cells in vitro, however only at millimolar concentrations, i.e. with potencies 106-108-fold lower than those of HMB-PP, thereby raising questions about their physiological relevance.

However, none of the known antigen-presenting molecules like MHC class I and II or CD1 are required for γδ T cell activation suggesting the existence of a novel presenting element.

Thus, the presence of a functional Vγ9/Vδ2 TCR appears mandatory for a response to non-peptidic antigens although the basis for the huge differences in bioactivity between closely related molecules like HMB-PP and IPP cannot be explained by conventional epitope presentation/recognition models.

It means that the stimulation with IPP or HMB-PP induces migration to the lymphatic tissues, specifically to the T cell area of lymph nodes.

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.

In most instances, the stimuli that trigger Vd1 expansion are not derived from pathogens but instead correspond to endogenous gene products presumably upregulated on infection.

A recent study of primary cytomegalovirus infection in infants found increased Vδ1 T cells that also expressed the typically NK cell associated markers NKG2C and CD57[28] A recent study has identified a specific subset of gut-resident Vδ1 IELs (intraepithelial lymphocytes) which express high levels of a natural cytotoxic receptor (NCR) which is NKp46.

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.

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.