It has been suggested that oral tolerance is mediated by CD8(+) T lymp
hocytes, but the functional properties of these cells are unclear. Her
e we show that the induction of tolerance by feeding mice ovalbumin (O
VA) does not prime antigen-specific class I MHC-restricted cytotoxic T
cells in vivo. Indeed, such responses are markedly suppressed in mice
fed OVA, and the induction of oral tolerance is abolished by depletio
n in vivo of CD4(+) but not CD8(+) T cells. These results indicate tha
t CD8(+) lymphocytes are unlikely to play a major role in the inductio
n of oral tolerance and are the first demonstration that specific cyto
toxic responses to an exogenous antigen can be suppressed by feeding a
ntigen.