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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.

Tolerance to human y-globulin (HGG) at the T cell level was readily induced in both normal and bursectomized FP and E L 6 strain chickens by intravenous injection of 5 to 50 mg of soluble HGG. T cells from tolerant chickens, subsequently immunized with HGG in complete Freund's adjuvant (CFA), failed to cooperate in the adoptive immune response to 2,4,6-trinitrophenylated (TNP) HGG with TNP-immune spleen cells. However, suppressive activity could not be demonstrated when cells from tolerant chickens were combined with cells from HGG and CFA-sensitized chickens in the recipients, even at a 5 : 1 ratio. HGG-specific helper activity could be induced, both in bursectomized FP and in intact EL6 spleen cells, but neither tolerant bursectomized nor tolerant intact chicken spleen cells showed suppressor activity in this assay. Such tolerant cells also failed to inhibit formation of helper cell activity upon transfer to intact or bursectomized recipients subsequently exposed to HGG and CFA. Cells mediating delayed hypersensitivity (TDH cells) were also tolerized by intravenous injection of soluble HGG. Injection of cyclophosphamide (CY), 100 mg/kg intraperitoneally, two days prior to the HGG did not interfere with this tolerance induction. CY also failed to augment the D H reactivity of immunized bursectomized animals, although it did increase the reactivity of intact animals. Thus, a CY-sensitive suppressor cell did not appear to be responsible for induction of the tolerant state. Moreover, spleen or thymus cells from tolerant bursectomized or intact animals, transferred into normal chickens, were unable to prevent sensitization of the TDH cells in recipients. This was true in both bursectomized and intact recipients and was also not affected by treatment of recipients with CY, used to facilitate entry of tolerant donor cells into recipients' lymphoid tissue. Tolerance was also readily induced in thymectomized chickens. It was considered unlikely that the generation of suppressor cells was responsible for induction of tolerance to HGG at the T cell level in bursectomized or intact chickens. Since antibody formation could be excluded as a factor in the bursectomized birds, these restills were in favor of a T cell deletion model of tolerance. Various ways in which delclioii of TDH cells might be achieved are discussed.

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