T cell tolerance in the chicken. II. Lack of evidence for suppressor cells in tolerant agammaglobulinemic and normal chickens.

Abstract

AbstractTolerance to human γ‐globulin (HGG) at the T cell level was readily induced in both normal and bursectomized FP and EL 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 DH 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 results were in favor of a T cell deletion model of tolerance. Various ways in which deletion of TDH cells might be achieved are discussed.