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Spleen cells from chickens injected with sheep erythrocytes (SE) intravenously 2 to 14 days prior to culture were found to give faster and higher plaque-forming cell responses upon addition of antigen on day 2 rather than on day 0 of culture. Cell mixture experiments showed that this was due to the induction of suppressor T cells upon re-exposure to SE on day 0 of culture. Spleen cells taken on days 2 or 14, but not between days 4 and 7 after priming to SE were sensitive to suppression. The suppressor cells were resistant to gamma irradiation (1000 rd) and to mitomycin C, but were apparently lost after 2 days of culture in the absence of antigen. Pokeweed mitogen addition on day 0 of culture also induced suppressor cells, both in SE immune and in normal spleen. Similar suppressor cells were induced in cultures of primed spleen cells taken from agammaglobulinemic chickens. The response to Brucella abortus in vitro was not affected by induction of suppression for the anti-SE response. Suppression could also be shown after transfer of cell mixtures to irradiated recipients. Helper cell activity for the anti-SE response could readily be shown, both in vivo and in vitro, in primed spleen cells precultured for 2 days in the absence of antigen, and was also resistant to 1000 rd gamma irradiation and to mitomycin C.

Presensitization of BX donors with B cells appears obligatory in order for their T cells to acquire suppressor capacity against the adoptive humoral antibody response of bursa cells to B. abortus. Although anti-Ig + C treatment of bursa cells removes their capacity to "immunize" BX chickens for suppressor activity, BX chickens cannot be sensitized for this effect by the injection of chicken IgM + IgG. Both embryonic and allogeneic bursa cells can "immunize" the T cells of BX chickens. The observation that spleen cells from BX chickens can cause absence of plasma cells and germinal centers in the spleen and mucosal lining of cecal tonsils of histocompatible recipients within 1-2 weeks after transfer suggests that the suppressor cells mediate their effect by acting directly on B cells at one or more stages during their development.

T cell-mediated delayed hypersensitivity (DH) to human gamma-globulin (HGG) can be induced in chickens by subcutaneous injection of the antigen in complete Freund's adjuvant (CFA). In the present work, it has been demonstrated that specific tolerance of the cells mediating this DH can readily be induced in both normal and bursectomized (BX) FP strain chickens by simple i.v. injection of soluble antigen, regardless of the presence of antibody production to the tolerogen. A significant degree of tolerance at the DH and helper T cell levels could be generated in BX birds by injection of as little as 0.5 mg of HGG; such a dose only induced tolerance in normal birds when it had been previously deagregated by ultracentrifugation. Regular, nondeaggregated antigen could produce tolerance in normal animals, but only at doses of greater than 5 mg. The tolerizing injection induced a primary antibody response in normal birds in all cases, but a secondary response could not be obtained in animals rendered tolerant at the T cell level. Establishment of tolerance appeared to be very rapid, and animals remained refractory to induction of DH for at least 3 weeks after the tolerizing injection. The mode in which the antigen was presented to the animals appeared to be crucial in determining whether tolerance or sensitivity would be established.