The functions of gamma delta T cells (γδT) are specific according to their location. It is observed that γδT cells express cytotoxic molecules- perforin,granzymes and FAS ligand. Chemokine receptors CCR5 and CXCR3 and adhesion molecules are also expressed by γδT cells. These γδT cells are considered as the first line of defense as they exhibit both activated and resting state. These are employed in effector functions.
Circulating γδT cells react rapidly with non-peptide antigen when they ING come across infection and hence activate innate immune cells finally activating adaptive immune response. Vδ2+ γδT cells are important for elimination of infections of microbial pathogens. Resident γδT cells have a role to play even in immune surveillance against malignancy. γδT cells can recognise molecules directly expression of cancer cells without Antigen presenting cells and presentation. These help in eliminating cells and hence participate in homeostasis. They also help in cytokine production.
(1) Wound Healing:
γδT cells constitute a major part of the T cell compartment in epithelial tissues. A special function can be noticed due to the correlation between T cell receptor (TCR) V gene and tissue localization. The γδ TCR which have Dentritic Epidermal T cells (DETCs) in murine skin produce cytokines and proliferate in response to damaged keratinocytes. This indicates a functional interaction between these two neighbouring cell types. The DETCs produce Keratinocyte growth factor- 1 (KGF) which is called fibroblast growth factor-7 following activation through γδ TCR. Fibroblast Growth Factor- 7 (FGF) along with KGF-2 (FGF-10) attach to FGFR2-IIIb receptor. Wound healing study in mice was essential and hence this was set up. The mouse of C57BL16 was wounded and later its location, morphology and density of DETCs were studied. After about 24-48 hours after wounding the DETCs which were spotted around the wound were changed in morphology and there shape was disfigured. Five days after wounding, the DETCs began to regain their dentritic morphology. Some DETCs were distant from the wound and these retained their normal shape. These DETCs are assumed to play a prominent role in tissue repair.
In order to check if the DETCs participate in wound repair, wild type and TCRδ-/- mice had a 2-3 day delay in wound closure in comparison to wild mice. Histology was seen and it was observed that there was reduced epithelial hyperthickening in TCRδ-/- mice compared to wild type mice, this showed keratinocyte proliferation and was impaired in the absence of γδ DETC. In order to confirm this, mice was injected with Bromodeoxyuridine (BrdU) at various intervals. Fewer BrdU positive cells were seen in wound edge in comparison to wound centre in TCRδ-/-. Hence it was seen that γδT cells play a prominent role in keratinocyte proliferation and reepitheliazation during healing. DETCs are activated through canonical Vγ3Vδ1 AND transgenic mice OT-1 were used. The BrdU complex was seen diminished and an expression identical Vα2Vβ5 TCR complexed with I-A b was seen. Hence it can be seen that DETCs contribute to wound repair via specific recognition of antigen through the Vγ3Vδ1TCR. It was also observed that KGFs are the major epithelial growth factors produced by DETCs. The FGF-7 experiment was examined in order to determine if γδ DETC are activated to produce FGF-7. DETCs are activated by their neighbours and damaged keratinocytes and these play a prominent role in wound repair by expressing KGFs and cytokines. Not much healing was observed in FGF-7-/- mice. The FGF-10 also could not be studied well as their life span is very small. When FGF-10 was produced in cell line 7-17 upon TCR simulation it was observed DETCs might participate in wound healing by production of FGF-10. Skin organ culture (SOC) assay was used to characterize γδ DETC produced factors to wound repair and keratinocyte proliferation and wound closure in TCRδ-/- mice can be attributed to lack of KGFs produced by DETCs. Wound healing is very complex and it involves epithelial cell proliferation, tissue deposition and inflammatory cell recruitment. Role of DETC in healing has been neglected. It has been however observed that mice which lack DETC actually have delayed wound healing. DETCs help in recognition of antigen and help in tissue repair by producing FGF-7 and FGF-10.
(2) Functions of epithelial and mucosal γδT cells :
Expression of insulin like growth factor 1 by DETCs have increased rates of epidermal apoptosis that can be rescued by addition of exogenous IGF-1 by DETCs hepl in expression of hyaluronan by keratinocytes. Hyaluronan is a glycosaminoglycan which is extruded into extracellular matrix and is involved in cell migration. Mice lacking γδT cells delay macrophage infiltration. All these effects are important in restoring epithelial homeostasis. γδT cells modulate inflammation during airway hyperresponsiveness. Depletion of αβT cells leads to decrease in Airway hyper responsiveness (AHR) and depletion of γδT cells increases the chances of disease.
The γδT cells are dependent on Vγ usage. V γ2+ T cells promote AHR whereas V γ2+ T cells suppress AHR. There is an inverse relation between t he number of γδT cells and neutrophills in lungs.
(3) Tumour :
γδTcells monitor the epithelial cells for malignant transformation. Human γδT cells lyse melanomas and other cancerous epithelial cells. There are too many debates regarding this study however.
Some γδ intraepithelial lymphocytes (IELs) are able respond to MHC1 related proteins but others for γδ IEL activation are believed to exist. In transplant patients there is suffering of CMV infection. These γδ IELs lyse CMV infected cells. A functional role for TCR in DETC activation by gram negative bacteria is seen. The role of γδT cells in homeostasis is very essential. The details of γδT cell development and mechanisms are important in maintenance and function which are becoming clear.
(4) Function of γδT cells in innate immunity :
γδT cells are sometimes considered as the first line of defense. The γδT cells form a whole lymphocyte system and develop in thymus. The mature γδT have many distinct features/subsets and have many effects on tissues. Recent studies have proposed that γδT cells have a role to play in both adaptive and innate immunity. Very little has been proved that mycoplasma species can elicit a γδT cell response but mycoplasma penetrans are capable of causing respiratory disease and these elicit a response in Variable (V)δ1+ and V δ2+ T cells. The ways in which mycobacterium induce γδT cells is not defined fully.
Self ligands of γδ TCR : Many ligands have the potential to indicate cellular stress these include - Cluster of differentiation 1 (CD), MIC-A or -B and F1-ATPase in humans and T10/22 in mice. F1 Adinoisine triphosphate (ATPase) is a mitochondrial antigen. Mitochondria are also considered a source of antigen for γδT cells. T22 is a considered ligand for γδT cell. The two studies which are Chien's group study and another group which studied MHCs suggest diversities of γδTCRs inspite of the ligands.
(a) There should be adjustments and fine tunning.
(b) Somatic changes affects TCR they will affect binding affinity.
Antigen presenting cells (APCs) serve in induction of antigen specific adaptive immunity. Antigen processing and presentation are innate functions. Activated human V γ9+V δ2+ γδT cells acquire these and APC becomes effective.
Many of the known TCR dependent activators of γδT cells were used. The γδT cells expressed lymph nodes. The increased expression of MHCII and induced primary responses of CD4+αβ T cells to Major Histocompatibility Complex II (MHC) antigen. These activated γδT cells and proliferated CD8+ and αβ T cells. γδT cells help in regulatory interactions with macrophages, granulocytes and dendritic cells.
It is clear that γδT cells play an important role in innate response but some information is still scarce. How do the specialized cells occur in small numbers, how is the development stage acquired and how do these get their function potentials. Some have connections with adaptive immune response too.
There are many other functions of gamma delta T cells which are not yet fully understood. Research on these are still going on.
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