Data provide evidence for a pathway that augments IFNγ secretion at sites of infection where gamma delta T cells are in abundance and where IFNγ may play a significant role in the control of the infection.Ī unique feature of T cells is their ability to discriminate between healthy and abnormal (infected or cancerous) cells in the body ( Feinerman et al., 2008). Thus, taken as a whole, these data show a differential regulation of NK and gamma delta T cells by different cytokines and differential regulation of activation functions within the gamma delta T cell population by combinations of several cytokines. Also, by contrast, a combination of IL-7 and IL-1 macrophage cytokines provide a strong proliferative signal and a relatively weak stimulus for the production of IFNγ by the IL-7/IL-1 combination. The investigators reported that this pattern of cytokine synergy differs from NK cells, where IL-12 functions in combination with IL-2 or TFNα to induce NK cells to produce IFNγ. Macrophage cytokines IL-12 and IL-1 function synergistically to provide a strong stimulus for significant IFNγ production by peritoneal γδ T cells, but they produce a relatively weak signal for proliferation. Skeen and Ziegler (1995) also showed that activation of γδ T cells for production of IFNγ is mediated by gut microbiota via macrophage-derived cytokines IL-1 and IL-12. Synthetic drug phosphoantigens and aminobisphosphonates also activate human Vγ9/Vδ2 T cells, which upregulate endogenous IPP/DMAPP ( Poupot and Fournié, 2004 Riganti et al., 2012 Sicard et al., 2005). Many microbes produce, in addition to IPP and DMAPP, the extremely active hydroxy-DMAPP (HMB-PP) and its corresponding mononucleotide conjugates ( Tyler et al., 2015). Human Vγ9/Vδ2 T cells, which make up a significant γδ T cell population in peripheral blood, are unique, as they specifically and rapidly respond to a set of nonpeptidic phosphorylated isoprenoid precursors, named phosphoantigens, the most common of these are isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate ( Tyler et al., 2015). However, the investigators reported that gamma delta T cells are not MHC-restricted and appear to be able to recognize whole proteins, rather than requiring peptides to be presented by MHC molecules on APCs, as with the conventional T cells. Skeen and Ziegler (1995) also reported that γδ T cells are found at sites of microbial infection and proliferate in response to bacterial antigens.

(1995) demonstrated in culture that resting γδ T cells recognize and respond to MHC class II determinants on allogeneic DCs in a manner that is highly dependent on the CD28 activation pathway as well as molecules such as CD2 and CD11a that mediate cell-to-cell adhesion. Molecules that activate γδ T cells are largely unknown, although Takamizawa et al.

Unlike most T cells that are characterized by their TCR having two glycoprotein chains, α and β-TCR chains, the TCR of γδ T cells are composed of one γ-chain and one δ-chain. Gamma delta T cells are a small subset of T cells making up about 2% of the total T cells in humans and mice, and are found predominately in the gut mucosa, within the intraepithelial lymphocytes. Bryan Tungland, in Human Microbiota in Health and Disease, 2018 4.2.7 Gamma delta T cells (γδ T cells)

Gamma lt vs or uberlayer