Immunosuppression caused by antigen feeding. I. Evidence for the activation of a feedback suppressor pathway in the spleens of antigen-fed mice.

Sheep red blood cells (SRBC) administered by the oral route to normal mice elicited no detectable splenic anti-SRBC plaque-forming cell (PFC) response until 8 weeks of antigen feeding. At this time a splenic IgA anti-SRBC PFC response was detected. On the other hand, spleen cells taken from mice given oral SRBC for 1-5 weeks showed striking changes in their in vitro anti-SRBC responsiveness as compared to spleen cells from normal mice. This was evidenced by enhanced early (days 3-4) in vitro responses, followed by suppressed late (day 5-6) in vitro responses. Both early enhancement and late suppression were T cell-mediated. Early enhancement appeared to be mediated by helper T cells of the Lyt-1+2.3- phenotype. Late suppression was also mediated by Lyt-1+2.3- cells, but Lyt-2-bearing cells had to be present in culture for suppression to occur. Lyt-2-bearing cells could be replaced with normal T cells. Furthermore, elimination of cells bearing I-J-encoded determinants from the T cell population isolated from the spleens of antigen-fed mice also partially relieved suppression. Thus, antigen feeding appears to activate a feedback suppressor pathway in which Lyt-1+2.3-, I-J subregion determinant-bearing T cells can suppress immune responses by causing normal T cells to become suppressor effectors. No evidence was found to show that antigen feeding induced Lyt-1-2.3+ suppressor cells in the spleen, nor were any serum suppressor factors detected.