Antigen-induced mucosal T cell activation is followed by Th1 T cell suppression in continuously fed ovalbumin TCR-transgenic mice

We investigated kinetics and dose-dependent features of mucosal and periphe ral immune responses following oral antigen application in a TCR-transgenic mouse model. Ovalbumin (OVA) TCR-transgenic mice were fed OVA at different doses (5-250 mg) and various frequencies tone to seven times, or continuou s feeding). Low- and medium-dose (10, 100 mg) OVA feeding resulted in primi ng of immune responses, i.e. increased antigen-specific proliferation as we ll as IL-2, IL-4 and IFN-1 secretion upon in vitro restimulation in Peyer's patches and spleen. Immune responses were suppressed with doses of one or three times 250 mg OVA feeding in the spleen. However, only the highest OVA feeding doses (7x250 mg OVA) or continuous feeding (5 mg daily in the drin king water over a 12-week period) actively suppressed immune responses and were associated with production of TGF-beta and IL-10 in the spleen and Pey er's patches. Thus, the cell population generated by continuous antigen fee ding was characterized by production of suppressive cytokines and seems to be based on a counter-regulation with Th1 cytokines. These data further def ine the regulation of suppressive immune functions following antigen feedin g in the periphery and the mucosal immune system.