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.