In vivo modulation of antigen-experienced cells in response to high-dose oral antigen: deletion but no evidence for alterations in the cytokine phenotype

Whether also antigen-experienced CD4(+) T cell populations undergo modulations upon oral antigen uptake supporting systemic unresponsiveness is still not fully understood. Using an adoptive transfer model with chicken ovalbumin (OVA)-specific T cells, we demonstrated that absolute numbers of transferred ex vivo-isolated CD4(+) memory T cells and in vitro-polarized T(h)1 cells considerably decrease within spleen and liver upon repetitive OVA feeding. As a consequence, these mice did not mount a delayed-type hypersensitivity reaction after OVA challenge. OVA-specific T(h)1 cells re-isolated from the liver showed augmented signs of apoptosis. However, there was no evidence that transferred effector or memory T cells acquired a regulatory phenotype, became anergic or underwent immune deviation. Our data suggest that oral antigen application does not induce alterations in the phenotype of CD4(+) effector and memory T cells. Instead, deletion of antigen-experienced CD4(+) T cells preferentially within the liver might be a major mechanism contributing to antigen-specific systemic unresponsiveness upon oral antigen uptake.