6 research outputs found
Preferential Th1 Cytokine Profile of Phosphoantigen-Stimulated Human VĪ³9VĪ“2 T Cells
Human VĪ³9VĪ“2 T cells recognise pyrophosphate-based antigens (phosphoantigens) and have multiple functions in innate and adaptive immunity, including a unique ability to activate other cells of the immune system. We used flow cytometry and ELISA to define the early cytokine profiles of VĪ³9VĪ“2 T cells stimulated in vitro with isopentenyl pyrophosphate (IPP) and (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate (HMB-PP) in the absence and presence of IL-2 and IL-15. We show that fresh VĪ³9VĪ“2 T cells produce interferon-Ī³ (IFN-Ī³) and tumour necrosis factor-Ī± (TNF-Ī±) within 4 hours of stimulation with phosphoantigen, but neither IL-10, IL-13, nor IL-17 was detectable up to 72 hours under these
conditions. Cytokine production was not influenced by expression or lack, thereof, of CD4 or CD8. Addition of IL-2 or IL-15 caused expansion of IFN-Ī³-producing VĪ³9VĪ“2 T cells, but did not enhance IFN-Ī³ secretion after 24ā72 hours. Thus, phosphoantigen-stimulated VĪ³9VĪ“2 T cells have potential as Th1-biasing adjuvants for immunotherapy
Cutting edge: CD1d restriction and Th1/Th2/Th17 cytokine secretion by human VĪ“3 T cells
Human Ī³Ī“ T cells expressing the VĪ“3 TCR comprise a minor lymphocyte subset in blood but are enriched in liver and in patients with some chronic viral infections and leukemias. We analysed the frequencies, phenotypes, restriction elements and functions of fresh and expanded peripheral blood VĪ“3 T cells. VĪ“3 T cells accounted for ~0.2% of circulating T cells, included CD4(+), CD8(+) and CD4(ā)CD8(ā) subsets, and variably expressed CD56, CD161, HLA-DR and NKG2D, but not NKG2A nor NKG2C. VĪ“3 T cells were sorted and expanded by mitogen stimulation in the presence of IL-2. Expanded VĪ“3 T cells recognised CD1d, but not CD1a, CD1b nor CD1c. Upon activation, they killed CD1d(+) target cells, released Th1, Th2 and Th17 cytokines and induced maturation of dendritic cells into APCs. Thus, VĪ“3 T cells are glycolipid-reactive T cells with distinct antigen specificities but functional similarities to natural killer T cells
Altered Distribution and Increased IL-17 Production by Mucosal-Associated Invariant T Cells in Adult and Childhood Obesity
Mucosal-associated invariant T (MAIT) cells are innate MHC-unrestricted cells that regulate inflammatory responses through the rapid production of cytokines. In this article, we show that circulating MAIT cells are depleted in obese adults, and depletion is associated with diabetic status. Circulating MAIT cells more frequently produced IL-17 upon stimulation ex vivo, a cytokine implicated in insulin resistance. MAIT cells were enriched in adipose tissue (AT) compared with blood. AT MAIT cells, but not circulating MAIT cells, were capable of producing IL-10. In AT from obese subjects, MAIT cells were depleted, were less likely to produce IL-10, and more frequently produced IL-17. Finally, we show that IL-17+ MAIT cells are also increased in childhood obesity, and altered MAIT cell frequencies in obese children are positively associated with insulin resistance. These data indicate that MAIT cells are enriched in human AT and display an IL-17+ phenotype in both obese adults and children, correlating with levels of insulin resistance. The alterations in MAIT cells may be contributing to obesity-related sterile inflammation and insulin resistance