title: Select plant tannins induce IL-2Ralpha up-regulation and augment cell division in gammadelta T cells.
abstract: Gammadelta T cells are innate immune cells that participate in host responses against many pathogens and cancers. Recently, phosphoantigen-based drugs, capable of expanding gammadelta 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 Vdelta2 subset of human gammadelta T cells. Vdelta1 T cells, the major tissue subset, are unaffected by phosphoantigen agonists. Using FACS-based assays, we screened primary bovine cells for novel gammadelta T cell agonists with activities not encompassed by the current treatments in an effort to realize the full therapeutic potential of gammadelta T cells. We identified gammadelta 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 Vdelta1 and Vdelta2 T cells and NK cells. Additionally, the extract greatly enhanced phosphoantigen-induced gammadelta T cell expansion. Our analyses suggest that a tannin-based drug may complement the phosphoantigen-based drugs, thereby enhancing the therapeutic potential of gammadelta T cells.
authors.affiliation: Veterinary Molecular Biology, Montana State University, Bozeman, MT 59718, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Holderness
authors.forename: Larissa
authors.initials: L
authors.lastname: Jackiw
authors.forename: Emily
authors.initials: E
authors.lastname: Kimmel
authors.forename: Hannah
authors.initials: H
authors.lastname: Kerns
authors.forename: Miranda
authors.initials: M
authors.lastname: Radke
authors.forename: Jodi F
authors.initials: JF
authors.lastname: Hedges
authors.forename: Charles
authors.initials: C
authors.lastname: Petrie
authors.forename: Patrick
authors.initials: P
authors.lastname: McCurley
authors.forename: Pati M
authors.initials: PM
authors.lastname: Glee
authors.forename: Aiyappa
authors.initials: A
authors.lastname: Palecanda
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jutila
mesh_terms: D000818:Animals; D020948:Cat's Claw / Q000737:chemistry; D002417:Cattle; D002455:Cell Division / Q000187:drug effects*; D005638:Fruit / Q000737:chemistry; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D027845:Malus / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000819:agonists* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes; D013634:Tannins / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D010936:Plant Extracts; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013634:Tannins