Select Plant Tannins Induce IL-2Rα Up-Regulation and Augment Cell Division in γδ T Cells

Abstract

γδ T cells are innate immune cells that participate in host responses against many pathogens and cancers. Recently, phosphoantigen-based drugs, capable of expanding γδ T cells in vivo, entered clinical trials with the goal of enhancing innate immune system functions. Potential shortcomings of these drugs include the induction of nonresponsiveness upon repeated use and the expansion of only the Vδ2 subset of human γδ T cells. Vδ1 T cells, the major tissue subset, are unaffected by phosphoantigen agonists. Using FACS-based assays, we screened primary bovine cells for novel γδ T cell agonists with activities not encompassed by the current treatments in an effort to realize the full therapeutic potential of γδ T cells. We identified γδ T cell agonists derived from the condensed tannin fractions of Uncaria tomentosa (Cat’s Claw) and Malus domestica (apple). Based on superior potency, the apple extract was selected for detailed analyses on human cells. The apple extract was a potent agonist for both human Vδ1 and Vδ2 T cells and NK cells. Additionally, the extract greatly enhanced phosphoantigen-induced γδ T cell expansion. Our analyses suggest that a tannin-based drug may complement the phosphoantigen-based drugs, thereby enhancing the therapeutic potential of γδ T cells.

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

“…cd T cells seem particularly responsive to certain nutrient properties found in various food and supplement products, especially those with high antioxidant values (Table 4). 69,[118][119][120][121][122][123][124][125][126][127] In a double-blind placebocontrolled randomized control trial, capsules containing fruit and vegetable concentrate (containing, among other compounds, standardized levels of b-carotene, vitamin C, vitamin E, folate and calcium) were given to law school students, taken as a representative of young adults living with modern day stresses, over a period of 11 weeks. 128 cd T cells were found to be specifically increased (by about 30%; no change in circulating ab T cells) in parallel to an increase in the antioxidant capacity of the study subjects, and in vitro analyses showed that this effect was associated with a more tempered inflammatory response upon phorbal myristate acetate stimulation.…”

“…One strategy that cd T cells use to fulfill the complex nature of their task is to creatively merge the instincts of Heat-treated mistletoe 125 Plant tannins; procyanidins (e.g. from unripe apple peels) 121,122,129 Polysaccharides from Acai berry and Yamoa 119,120 Concord grape juice and fruit/vegetable concentrate 126,128 Aged garlic 124 Biography of human cd T cells S Kalyan and D Kabelitz 26 the innate with the diversity of the adaptive immune systems. Thus, some of the antigens that they recognize are evolutionarily shared by the self and non-self and their subsequent response is contextually guided by the level of distress that they sense from within-often in the context of the contingent presence of other damage-associated molecular patterns.…”

Developing a conceptual model of possible benefits of condensed tannins for ruminant production

“…limphokines) produced by epithelial uterine lymphocytes induce regulatory dynamics on IFN-τ and IFN-γ (Oliveira et al, 2012). However, although the function of γδ T-lymphocyte on early maternal − embryonic and embryonic − foetal interfaces is not clear, Holderness et al (2007) and Jutila et al (2008) suggested that CT (i.e. trimers and complex oligomeric-CT; Holderness et al, 2007) are prominent γδ T-lymphocyte agonists.…”

“…However, although the function of γδ T-lymphocyte on early maternal − embryonic and embryonic − foetal interfaces is not clear, Holderness et al (2007) and Jutila et al (2008) suggested that CT (i.e. trimers and complex oligomeric-CT; Holderness et al, 2007) are prominent γδ T-lymphocyte agonists. Therefore, it may be possible that after ruminal fermentation, the CT molecule, the CT-protein bound fractions or CT-like compounds act on lymphocyte T-cell receptors, cytokine and chemokine synthesis and/or secretion to engage signal transduction.…”

“…maternal blood circulation; Majewski et al, 2001;Oliveira et al, 2012). In immune-modulating in vitro assays (Holderness et al, 2007) with apple CT (i.e. procyanidin-type polymer), bovine CD8 + and γδ T-lymphocytes demonstrated cell proliferation via upregulation of the interleukin (IL)-2Rα chain expression and possibly endogenous concentration of phosphoantigens (Holderness et al, 2007) and IFN-γ secretion (Percival et al, 2008).…”