Antigen presentation by parenchymal cells: a route to peripheral tolerance?

T-cell activation and the development of efficient immune responses require s the delivery, by the antigen-presenting cell, of two distinct signals. Th e first results from the engagement of the TCR:CD3:CD4 complex, and the sec ond from the interaction of CD28 with the B7 family of co-stimulatory molec ules. In this context, the physiological significance and the functional co nsequences of antigen presentation by B7-deficient parenchymal cells, which express MHC class II molecules as a result of inflammation, remains a matt er of debate. In this paper we have attempted to critically review the ofte n conflicting reports on the functional effects of antigen presentation by epithelial and endothelial cells to T cells, both in vitro and in vivo. Our own findings are summarised in a model which is consistent with the sugges tion of an important role for antigen presentation by parenchymal cells in the induction and the maintenance of peripheral tolerance.