Mice fed sheep erythrocytes (SRBC) or horse erythrocytes (HRBC) for 2 or more weeks could not produce significant delayed-type hypersensitivity (DTH) reactions to the specific erythrocyte used for feeding. Diminished DTH reactions persisted for at least 6 months after feeding was stopped. Although DTH was diminished in vivo, cells sensitized for DTH as well as suppressor cells could be detected in the spleens of SRBC-fed mice. The presence of spleen cells sensitized for DTH was revealed by the transfer of spleen cells from SRBC-fed mice direactly into the footpads of normal mice followed by local SRBC challenge. The presence of suppressor cells was shown by i.v. transfer of spleen cells from SRBC-fed to normal mice. DTH reactions were not suppressed by the transfer of mesenteric lymph node cells, Peyer's patch cells, or serum from fed to normal mice. Spleen cells from fed mice inhibited the production of DTH when transferred into normals before sensitization with SRBC. However, spleen cells from fed mice did not inhibit elicitation of the DTH response when transferred into mice with established DTH immunity. Further, spleen cells sensitized for DTH transferred positive DTH reactions equally well to SRBC-fed and normal mice suggesting that suppression of DTH after SRBC feeding was not mediated by effector blockade. It is clear that immune responses in extraintestinal sites can be altered by exposing the host to antigens by the intestinal route. Therefore, it should be possible to manipulate specifically certain systemic immune responses by antigen-feeding.

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