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

Abstract

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.

Specific In Vitro IgM Responses of Human B Cells: A Complex Regulatory Network Modulated by Antigen

“…Although the role of SSA is unclear, it is conceivable that SSA may play a role in the perpetuation of the disease. This would be reminiscent of findings in bursectomized birds, where transplantabie suppressor T-cells were consistently detected (Blaese et al 1974, Grebenau & Thorbecke 1978. Together with the recent finding in similar patients of normal numbers of pre-B-cells expressing cytoplasmatic immunoglobulin (Vogler et al 1976, Pearl et al 1978, our data suggested that B-lymphocytes in these patients may be inherently able to complete at least some early steps in differentiation such as those required for IgM antibody responses.…”

“…Some characteristics of this PFC response are summarized in Table XIL In striking contrast to normals, patient PFC precursor cells did not bear slg determinants. This would be reminiscent of findings in bursectomized birds, where transplantabie suppressor T-cells were consistently detected (Blaese et al 1974, Grebenau & Thorbecke 1978. Another surprising difference was the observation that the addition of the T-cell mitogen PWM resulted in suppression of patient, but not the normal PFC response.…”

Enhancing Effect of Surgical Bursectomy on Antibody Response

“…33). Another explanation might be that suppressor T cells fail to proliferate in the absence of certain B cells or of B cell products ( 16). This alternative would particularly apply for anti-idiotype suppressor T cells.…”