LYMPHOCYTES FROM ORALLY TOLERIZED MICE DISPLAY ENHANCED SUSCEPTIBILITY TO DEATH BY APOPTOSIS WHEN CULTURED IN THE ABSENCE OF ANTIGEN IN-VITRO

The mechanism responsible for the induction of immunological tolerance by oral administration of soluble antigen remains unclear. Here we sh ow that, when cultured in vitro in the absence of antigen, lymphocytes from mice tolerized with a single feed of 25 mg of ovalbumin display an enhanced mortality in comparison with cells from immunized control animals. This increased cell death affects both CD4(+) and CD8(+) T-ly mphocyte subsets, and morphological and flow cytometric analyses sugge st that it occurs via apoptosis. All of the changes associated with th e propensity of tolerant cells to die by apoptosis in vitro are reduce d by the inclusion of the tolerizing antigen in the cultures. These re sults suggest that tolerance to dietary proteins is accompanied by fun ctional changes in T lymphocytes that render them susceptible to apopt osis. This mechanism may underlie the profound and permanent tolerance to food antigens found under physiological conditions and may provide a useful basis for immunotherapy.