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Gamma Delta T Cells and Their DevelopmentBY: Preethi Venkateswaran | Category: Biology | Submitted: 2011-03-31 19:00:08
Gamma Delta T Cells: Gamma Delta T cells are a part of the T cells and they have a distinct T Cell Receptor (TCR) on the surface. The B and T lymphocytes are different from each other cause of their ability to interact with a wide variety of antigens. The TCR and Immunoglobulin help in specific interaction. Most of the T cells have T cell receptors having glycoprotein chains composed of alpha and beta TCR chains. On the other hand in gamma delta T cell the TCR has 1 gamma and 1 delta chain. This is less common than the alpha and beta chains but present largely in the mucosa. Both alpha beta and gamma delta were heterodimers associated with transduction complex. It was seen that the gamma delta (γδ) chains form another class of recognition structure. Features of the γδ T cells: • Both the γδ and αβ T cells represent two distinct lineages. • γδ T cells can be divided into several subpopulations. (a) Their stage of development in the progeny (b) Sets of γ and δ genes they use to form receptors. (c) Extent of VDJ or VJ diversity. • Pairing of the γ chains and δ chains results from an intrathymic or peripheral expansion of the lymphocytes expressing γδ combination. The antigen repertoire of γδ T cells does not express CD4 or CD8 molecules. Their absence from the surface of γδ lymphocytes makes us aware that these cells allow recognition of antigen in its naïve form. Development of γδT Cells: The thymus gives rise to both MHC restricted αβT cells and the non MHC restricted γδT cells. The αβT cells consist of both CD8 αβ+ and CD4 T cells. The γδT cells have both CD8+ and CD4+. The γ chain is located in chromosome 7 with 14 V regions, 5 J regions and 2 C regions. On the other hand the δ chain is located in chromosome 14 with 3 V regions, 3 D regions, 3 J regions and 1 C region. The γδT cells are responsible for Primary Immune response and they also help in wound healing, tumour surveillance and immunoregulation. The TCR γδT cell is well conserved which is noticed predominantly in fish and other mammals. The gene utilisation however is different in all of the species. In humans it is low in presentation even then they help us fight against the infections and pathogens. The γδT cell biology and evolution is totally different. These do not follow the αβT cells. The γδT cells help to define an evolutionary mode of T cells development. The γδT cells present in murine populate the different tissues automatically. The fate of the γδT or the αβT progenitors can be determined by the signals they send or emit. The development of the αβT or γδT is interdependent. These cells are positively selected rather than they are negatively selected. The gut γδT cells are extrathymically developed. γδ/αβ T cell fate is determined early in the T cell development independent of the TCR. Study of mice support this theory and they tell us about the rearrangement of the TCR α, TCR γ and TCR δ transgenes along with the thymic precursors. The γδ compartment was comparable to only the TCR γδ. On the other hand the αβ compartment can be studied only by TCR β. Hence these could express both TCR γδ and the pre TCR but this had little towards the contribution of the development of these cells. A selective lineage was studied. Pro T cells from the young mice were separated into IL-7Ra+ and IL-Ra -10 to generate γδ cells or αβ committed DP cells. This was analysed for 11 days. Both subsets gave rise to the γδ cells and DP (double positive) cells but IL-7 Rα+ pro-T cells showed a five fold higher potential to develop into γδ cells. IL-7 and IL-7R promotes rearrangement at the TCRγ locus and enhanced expression of TCRγ. Notch signalling: Notch is a cell signalling pathway present in multi cellular organisms. This occurs primarily in metazoans. Attractive candidate for a TCR-independent role in cell fate determination are notch transmembrane receptor. When the notch is ligated by Jagged or Delta like proteins, its intracellular domain is cleaved off and translocates to the nucleus where it modulates transcription, at least in part via interaction with the DNA-binding protein RBP-J. It is clear that Notch-1 signalling in response to the thymic microenvironment promotes T cell lineage commitment at the expense of B-cell development. The notch driven promoters and their deficiencies have been studied by using various techniques. Notch transmembrane receptor Notch 1+/- reportedly favoured γδ T cell development when compared to notch +/+ BM and the recent studies are a proof of this. The instructive model: The TCRγδ and the pre TCR provide distinct signals which influence an uncommitted progenitor to adopt either a γδ or αβ T cell fate. Several other databases indicate that the that postnatal αβ T cells and their progenitors are depleted of productively rearranged TCRγ and TCRδ genes, whereas this is not the case in mice that can rearrange TCRδ gene segments but in which the delta chain is non-functional. These databases are a proof to say that the gamma delta T cell receptor is not neutral in αβ cell but opposes in the development of the αβ cell. Certain γδ TCRs are first expressed as proteins in DN4 stage and TCRβ appears one stage earlier which is DN3. So it becomes difficult to understand the development of gamma delta T cell development with the signalling pathway. Signalling Potential Model: This was a refinement of the instructive model but here if the signal was strong then it delivered TCRγδ cell. If it was weak then it was TCRαβ. Reducing TCRγδ signalling potential in a TCRγδ transgenic mouse by replacing TCRz chain with a TCRz chain that lacked any of its 3 immunoreceptor thyrosine based activation motifs reduced γδ T cell development and increased αβ T cell commitment. Regulation of γδ T cells differentiates from αβ T cell progenitors. The γδ T cells which distinguish γδ population from αβ cells were described. This was shared by TCRαβ+ CD8α+ cells showing functional potential of a T cell. There was failure of experiment of γδ biased gene profile and this was due to lack of DP cells. TCR selection of γδ T cells: The TCR γδ is required to generate γδ cells, γδ separate selection is controversial. Presence of ligand in T 105/T22b mice results in G8-TCR γδ expressing γδ cells homing to the gut and adopting characteristics of the TCR γδ and IELs. Positive or negative selection of T cell depends on context of the cell. The steady state of γδ cells can be evident from several genetic experiments. The stage at which DETC maturation ceases in the thymus is strain-dependent and reportedly mediated by thymic radiosensitive cells. These two studies strongly suggest that DETC maturation depends on thymic selection events. It was therefore concluded that many non-Vg5+ DETCs express TCRs with highly related structures, which is unprecedented in normal mice. This suggested selection occurs on the basis of the TCR. The DETCs can be divided into two classes Vδ5+Vδ1- DETCs which are dentritic and normal. The other group is Vγ5-Vδ1- DETCs which are not dentritic nor are they normal. Article Source: http://www.biotecharticles.com/ About Author / Additional Info: A growing scientific writer. Comments on this article: (0 comments so far)
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