Regulation of Cytokine Production by γδ T Cells

Abstract

A minority of peripheral blood T lymphocytes used heterodimeric T cell receptor (TCR) composed of a Vγ9 chain associated with Vδ2. These circulating Vγ9Vδ2 γδ T cells mainly recognize low-molecular-mass non-peptide antigens derived from microbes and plants in a MHC-unrestricted manner. Furthermore, they produce rapidly after antigen contact cytotoxic molecules and cytokines, thereby activating innate immune cells, facilitating adaptive immune responses of αβ T cells, protecting the host against infections with certain microbial pathogens, and playing a role in tumor defense. Another γδ T cell subset underrepresented in the peripheral blood expresses Vδ1 chain associated with variable Vγ elements and comprises the major γδ T cell population in epithelial tissues such as the small intestine. Homologous γδ T cells are found in the mouse in vagina, uterus, lung and skin. Vδ1 γδ T cells mainly recognize antigens restricted to certain cell types of epithelial origin, which are induced upon stress, infection, inflammation and tumor growth, and thus play a role in immunosurveillance against malignancy, pathogen eradication, and wound healing. Several reports suggest that γδ T cells are immunregulatory cells, interacting and modulating the activity of other immune cells directly or by cytokine production. Here we summarize the current knowledge on the role of cytokines produced by γδ T cells and their ability to influence and regulate other cells of the immune system.

Modulation of γδ T cell responses by TLR ligands

“…Vd2-and Vd1-expressing cd T cells are presented only in small numbers in peripheral blood of humans, whereas Vd1-expressing cd T cells are relatively abundant in intestine, skin epithelia, and uterus of humans. Under pathological conditions, cd T cells can quickly expand and infiltrate into lymphoid compartments and other tissues [1,3,4]. Human Vd2 cd T cells recognize phosphorylated intermediates of the non-mevalonate pathway of bacterial isoprenoid biosynthesis pathway, whereas Vd1 cd T cells recognize stress-inducible MHC class I chain-related antigens (MIC) A/B or self-lipid presented antigens by CD1c [5][6][7].…”

“…Human Vd2 cd T cells recognize phosphorylated intermediates of the non-mevalonate pathway of bacterial isoprenoid biosynthesis pathway, whereas Vd1 cd T cells recognize stress-inducible MHC class I chain-related antigens (MIC) A/B or self-lipid presented antigens by CD1c [5][6][7]. Both cd T cell subsets rapidly release IFN-c, TNF-a, MIP-1a/b (CCL3/4), RANTES (CCL5), and granzymes after TCR stimulation, thereby activating other cells of the immune system [4]. There are alternative nomenclatures for murine Vc/Vd genes in this review.…”

Direct Costimulatory Effect of TLR3 Ligand Poly(I:C) on Human γδ T Lymphocytes

“…These cells primarily recognize phosphorylated intermediates of the nonmevalonate pathway of the bacterial isoprenoid biosynthesis pathway (phosphoantigens) (3,4) and thus sense microbial infection at a very early stage. After ligand recognition, ␥␦ T cells rapidly release cytokines such as IFN-␥ and TNF-␣, thereby activating innate immune cells and facilitating adaptive immune responses by ␣␤ T cells (1,5). Therefore, it is assumed that ␥␦ T cells may serve as protection against infections as a first line of defense before Ag-specific ␣␤ T cells expand.…”