Plant-derived flavonoids are inhibitors of various intracellular processes, notably phosphorylation pathways, and potential inhibitors of cellular autoimmunity. In this study, the inhibiting effects of various flavonoids on antigen-specific proliferation and interferon-gamma (IFN-γ) production by human and murine autoreactive T cells were evaluated in vitro. T-cell responses were evaluated for the human autoantigen alpha B-crystallin, a candidate autoantigen in multiple sclerosis, and for the murine encephalitogen proteolipid protein peptide PLP (139-151). The flavones apigenin and luteolin were found to be strong inhibitors of both murine and human T-cell responses while fisitin, quercitin, morin and hesperitin, members of the subclasses of flavonoles and flavanones, were ineffective. Antigen-specific IFN-γ production was reduced more effectively by flavones than T-cell proliferation, suggesting that the intracellular pathway for IFN-γ production in T cells is particularly sensitive to flavone inhibition. These results indicate that flavones but not flavanoles or flavanones are effective inhibitors of the potentially pathogenic function of autoreactive T cells. The effects of flavones were the same for human and murine autoreactive T cells, stressing the usefulness of animal models of autoimmunity for further studies on the effects of flavonones on autoimmune diseases. © 2004 Elsevier Inc. All rights reserved. Chemicals / CAS: apigenin, 520-36-5; crystallin, 11046-99-4; gamma interferon, 82115-62-6; hesperetin, 520-33-2; luteolin, 491-70-3; morin, 480-16-0; quercetin, 117-39-5; antigen-specific helper factors; Apigenin, 520-36-5; Flavonoids; Interferon Type II, 82115-62-6; Luteolin, 491-70-3; Lymphokines