Effect of carrier specific tolerance on the generation of helper cell function

The effect of carrier specific tolerance on the development of helper cell function was studied in irradiated rats reconstituted with normal or carrier tolerant bone marrow. Bone marrow (BM) from normal rats or rats tolerant to sheep IgG (SGG) was transferred to lethally irradiated syngeneic recipients, which were challenged 3 to 5 weeks later when immunocompetence to T dependent antigens was shown to have recovered. When recipients were challenged with the 2,4,6 trinitrophenyl (TNP) hapten coupled to SGG in adjuvant, groups which received SGG tolerant BM were 70-80% unresponsive in terms of anti TNP plaque forming cells compared to recipients of normal BM. This effect was carrier (SGG) specific and was reversed when normal thymocytes were transferred with tolerant BM. Moreover, neither tolerant BM nor tolerant thymocytes were able to suppress the responsiveness of normal BM at a 1:1 ratio. These cell mixing experiments imply that the reduction in helper cell function is due neither to suppressor cells nor antigen carryover in the tolerant BM. It is suggested that a BM precursor of the helper T cell may be rendered tolerant and therefore already possesses antigen specificity prior to thymic migration.