Antigen-specific T cell activation and proliferation during oral toleranceinduction

One of several routes of achieving immunologic tolerance is through functio nal inactivation of Ag-specific T cells. Oral administration of Ag can allo w survival of the Ag-specific T cells that are functionally anergic, The ai m of this study was to investigate whether functional inactivation of Ag-sp ecific T cells is directed through an activation process and to further def ine the differentiative pathways and functional characteristics of anergic T cells. Mice were transplanted with OVA-specific TCR-transgenic T cells an d either fed OVA or immunized s.c. with the OVA peptide 323-339 in CFA, OVA -specific T cells from OVA-fed mice were unresponsive to restimulation in v itro within 48-72 h after treatment. In vivo, however, T cell proliferation was detected by 5,6-carboxy-succinimidyl-fluoresceine-ester intensity chan ges in OVA-specific T cells. The mesenteric lymph nodes (LNs) from OVA-fed mice more frequently contained OVA-specific dividing cells in vivo than tho se in the peripheral LNs, and the reciprocal was observed following s.c. im munization of the OVA peptide in CFA, The induction of anergy in OVA-fed mi ce was accompanied by rapid up-regulation of CD69 and CTLA-4, later down-re gulation of CD45RB on OVA-specific T cells, and a marked decrease in T cell secretion of IL-2, IL-10, and IFN-gamma after OVA restimulation in vitro. Results from this study indicate that the inductive phase of oral tolerance is preceded by Ag-specific T cell activation in vivo, proliferation in the regional draining LNs, and differentiation into a memory-like state. These results indicate that Ag directed differentiation occurs as a part of T ce ll tolerance through anergy.