Direct measurement of anergy of antigen-specific T cells following oral tolerance induction.

T cell tolerance induced by oral administration of Ag may be the result of either deletion or functional inactivation of Ag-specific T cells. OVA p(323-339)-specific TCR transgenic (Tg+) lymphocytes were transplanted into BALB/c recipients. Chimeric mice were fed OVA and subsequently challenged with the peptide in CFA. Tolerance was then assessed by measurement of lymph node (LN) cell proliferation in response to the peptide, and deletion was assessed by measuring the frequency Tg+ T cells by flow cytometry. Lymphocytes from chimeric mice fed OVA showed a dose-dependent decline in their proliferative response to the peptide in vitro, compared with immunized control mice that were not fed OVA. Calculation of proliferative potential per Tg+ cell demonstrates that nonresponsiveness due to feeding Ag results in the induction of anergy in the LN. In addition, analysis of intestinal intraepithelial lymphocytes following feeding of OVA did not show evidence of trafficking of LN T cells to the small intestine intraepithelial nor lamina propria compartments.