Induction of memory and effector suppressor T cells by perinatal exposure to antigen

Abstract

The development of tolerance and suppression after perinatal exposure to antigen was studied to clarify the role of suppressor cells in self tolerance. Deaggregated human gamma globulin (dHGG) was administered transplacentally to fetal mice by injecting their mothers at various stages of pregnancy. Other mice were exposed to dHGG present in the colostrum of foster mothers previously injected with dHGG. Nonspecific suppression was seen on adoptive transfer of spleen cells from all donors less than six weeks of age. After that time, HGG-specific primary suppression by Ly-1-2,3+Ia+ T cells was detected in all animals exposed to dHGG either pre- or postnatally and persisted for up to three months. In addition, recall of specific memory suppression by antigen challenge was demonstrable for up to six months. Tolerance, on the other hand, was generated only by higher doses of dHGG in utero and was relatively short-lived when compared to suppression. The short duration of tolerance could not be attributed to the generation of T helper cells, since no significant HGG-specific helper activity was detected after perinatal exposure to HGG; rather it was thought to be due to the failure of small doses of dHGG to generate sufficient effector T suppressor (Ts) cells to inactivate the continually increasing number of HGG-specific B cells being generated during ontogeny. Since perinatal tolerance to HGG is known to be prolonged by repeated exposure to antigen, this model implies that the maintenance of natural self tolerance is Ts cell dependent and requires the continued presence of antigen.