Abstract
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.
Highlights
CD4+ T cells are distributed throughout the body, in lymphatic organs such as the spleen and lymph nodes, and they play an important role in the adaptive immune system
Because CD4+ T cells greatly contribute to antigen-specific cell proliferation and IL-2 production from the splenocytes of DO11.10 mice, we investigated the effects of Apple Procyanidins (APCs) on activated CD4+ T cells
CD4+ T cells separated from the splenocytes of DO11.10 mice were activated following T cell receptor (TCR) stimulation by an anti-CD3ε monoclonal antibody in the presence of APCs (0, 6.25, 12.5, or 25 μM)
Summary
CD4+ T cells are distributed throughout the body, in lymphatic organs such as the spleen and lymph nodes, and they play an important role in the adaptive immune system. T cell receptor (TCR)-mediated signaling by specific antigens first promotes the expression of interleukin (IL)-2, which is the most important cytokine for the activation and proliferation of T cells. Mitochondrial metabolism, not glucose metabolism, is essential for IL-2 expression, effector functions depend on glycolytic activity [1,2,3,4]. A previous study indicated that oligomeric procyanidins prevent the aggravation of clinical symptoms and suppress antigen-specific immune responses in experimental autoimmune encephalomyelitis [9]. Procyanidins might modulate immune system functions, but the comprehensive mechanism of their pharmacologic effects on the immune system is unclear. We investigated the immune-modulating effects of apple derived procyanidins and oligomeric procyanidins to clarify the pharmacologic mechanism of procyanidins in the activation of primary CD4+ T cells
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