Antigens in tea-beverage prime human Vγ2Vδ2 T cellsin vitroandin vivofor memory and nonmemory antibacterial cytokine responses

Abstract

Human ␥␦ T cells mediate innate immunity to microbes via T cell receptor-dependent recognition of unprocessed antigens with conserved molecular patterns. These nonpeptide alkylamine antigens are shared by tumor cells, bacteria, parasites, and fungi but also by edible plant products such as tea, apples, mushrooms, and wine. Here we show that priming of ␥␦ T cells with alkylamine antigens in vitro results in a memory response to these antigens. Such priming results also in a nonmemory response to whole bacteria and to lipopolysaccharide, characterized by IL-12-dependent secretion of IFN-␥ by ␥␦ T cells and by ␥␦ T cell proliferation. Drinking tea, which contains L-theanine, a precursor of the nonpeptide antigen ethylamine, primed peripheral blood ␥␦ T cells to mediate a memory response on reexposure to ethylamine and to secrete IFN-␥ in response to bacteria. This unique combination of innate immune response and immunologic memory shows that ␥␦ T cells can function as a bridge between innate and acquired immunity. In addition, these data provide an explanation for the health benefits of tea. In humans, ␥␦ T lymphocytes comprise 2-5% of peripheral blood T cells, and the majority (V␥2V␦2 T cells) coexpress V␥2 (alternatively named V␥9) and V␦2 T cell receptor (TCR) subunits. Found only in primates, this junctionally diverse yet functionally uniform population of T cells recognizes unprocessed, nonpeptide antigens with conserved molecular patterns such as alkylamines (1) and organophosphates (2, 3) in a TCR-dependent manner without MHC or complementaritydetermining region 1 (CD1) restriction (1, 4). One such alkylamine, ethylamine (EA), is found in brewed tea as an intact molecule and in its precursor form, L-theanine (5, 6). Tea (Camellia sinensis) has been touted as a healthful and medicinal beverage for centuries, and research has focused on the antioxidant activity of the catechins (7,8). However, no in vivo data demonstrating an immunologic effect of tea on human tissue have been published.There is now a large body of evidence supporting the role of ␥␦ T cells in resistance to infection. In mice, studies using specific ␥␦ T cell mAbs and ␥␦ T cell knockout mice provide compelling evidence for antimicrobial roles against bacterial, parasitic, and viral infection (9-13). In humans, ␥␦ T cells expand up to 50-fold in the peripheral blood 6-10 days after infection with a wide array of bacterial, viral, and parasitic microbes (14-18). These ␥␦ T cell expansions can be recapitulated in vitro by exposure of peripheral blood mononuclear cells (PBMCs) to purified nonpeptide microbial products (alkylamines and organophosphates) and pharmacologic agents that mimic bacterial antigens such as nitrogen-containing bisphosphonates as well as heat-killed bacteria and parasites, bacterial or parasitic extracts, and virusinfected cells (19)(20)(21)(22). Using a severe combined immunodeficiency mouse reconstituted with human PBMCs model, we showed that the presence of human ␥␦ T cells is necessary for survival during infection by Es...

Enhancement of Antigen-Specific Immunoglobulin G Production in Mice by Co-Administration of L-Cystine and L-Theanine

“…In the L-theanine single-administration group, Th1 was dominant 24 hr after antigenic stimulation. As ethylamine, a metabolite of L-theanine, induces secretion of Th1 cytokines from γδT cells [4,15], it is possible that this enhancement is due to cell-mediated immunity in the L-theanine single-administration group. This also exhibits the different effects of co-administration and single administration of L-theanine.…”

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.…”

Detection of Cell Surface Ligands for the γδ TCR Using Soluble TCRs

“…Moreover, a number of studies suggest that ␥␦ TCRs instead or in addition are specialized to recognize common microbial Ags. These include a group of small organic compounds dubbed phosphoantigens that stimulate human V␥9/V␦2 ϩ cells (33), as well as certain alkyl amines (34,35). The question of which stimuli represent ligands for a ␥␦ TCR is complicated by findings showing that ␥␦ T cell responses can also be evoked through receptors other than the TCR (36 -40).…”