Oligomeric Procyanidins Interfere with Glycolysis of Activated T Cells. A Novel Mechanism for Inhibition of T Cell Function.
Procyanidins, which are flavonoids that are found in a variety of plant species, reduce or prevent immune disorders, such as allergy and autoimmune diseases, through an unknown mechanism. In the present study, we investigated the effects of procyanidins on the T cell receptor (TCR)-mediated responses of CD4⁺ T cells in vitro. Apple procyanidins strongly suppressed the proliferation of splenic CD4⁺ T cells that were stimulated by an anti-CD3ε antibody, as well as splenocytes stimulated by antigen, but did not alter interleukin (IL)-2 secretion from these cells. Furthermore, we found that oligomeric procyanidins strongly suppressed, in a degree of polymerization dependent manner, the proliferation of activated CD4⁺ T cells, as well as their production of effector cytokines, including glycolysis associated-cytokines, without affecting IL-2 secretion. Additionally, we investigated the inhibitory effects of oligomeric procyanidins on the glycolytic activity of activated CD4⁺ T cells. We show that pentameric procyanidin suppressed L-lactate production and glucose uptake in activated CD4⁺ T cells. These results suggest that oligomeric procyanidins suppress the functions of activated CD4⁺ T cells by interfering with glycolysis.
National Food Research Institute, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan. masaogot@affrc.go.jp.
Masao
M
Goto
National Food Research Institute, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan. mana5998bu@affrc.go.jp.
Manabu
M
Wakagi
Institute of Fruit Tree Science, National Agriculture and Food Research Organization, 2-1 Fujimoto, Tsukuba, Ibaraki 305-8605, Japan. tshoji@affrc.go.jp.
Toshihiko
T
Shoji
National Food Research Institute, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan. yuko@affrc.go.jp.
Yuko
Y
Takano-Ishikawa
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006019:Glycolysis / Q000187:drug effects*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D027845:Malus / Q000737:chemistry*; D051379:Mice; D044945:Proanthocyanidins / Q000737:chemistry / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000975:Antioxidants; D044946:Biflavonoids; D007376:Interleukin-2; D044945:Proanthocyanidins; D011948:Receptors, Antigen, T-Cell; C017674:procyanidin; D002392:Catechin
T cell; activation; glycolysis; interleukin-2; procyanidin; proliferation