Immunological tolerance: High-dose antigen-induced suppressor cells from tolerant animals inactivate antigen-presenting macrophages

Abstract

Studies were carried out to characterize the target cell for the activity of suppressor cells induced in highzone tolerance to deaggregated human gamma globulin (HGG). We applied an in vitro system for the initiation of an immune response, consisting of culturing spleen Iymphocytes on HGG-fed macrophages, in which initiator T cells are generated.These cells, when injected into the foot pads of syngeneic mice, recruit specific anti-HGG effector T Iymphocytes. We Although all three models are strictly antigen-specific, the third model suggests that even though the induction of the block by the suppressor T cells is antigen-specific, the suppressprs should paralyze the induction of an immune response to an unrelated antigen provided the latter is taken up and exposed by the same macrophages that were fed with the tolerogen.We applied a system in which the effects of suppressor cells can be tested during the first steps of induction of a primary T cell-dependent immune process, namely, on the level of macrophage-T cell interaction. We studied the capacity of spleen cells derived from tolerant animals to prevent the in vitro macrophage-mediated "education" of antigen-specific initiator T lymphocytes. We indicate that suppressor cells derived from HGG-tolerant animals exert their suppressive activity by injuring the macrophages presenting the tolerogen. MATERIALS AND METHODSMice. In all of our present experiments, 3-month-old BALB/c female mice were used. These mice were supplied by the Animal Breeding Center of the Weizmann Institute of Science.Adult thymectomy was performed at the age of 6 weeks and mice were tested 2 months later.Chemicals and Media. Dulbecco's modified Eagle's medium and Dulbecco's phosphate-buffered saline (Pi/NaCI) (pH 7.4) were supplied by the Cell Biology Department. RPMI 1640 was purchased from GIBCO. All culture media were supplemented with penicillin (100 units/ml), streptomycin (100 mg/ml), gramamycin (40 Mg/ml), sodium bicarbonate (24 mM), and 2-mercaptoethanol (50,MM). 2-Mercaptoethanol was purAbbreviations: HGG, human gamma globulin; HRS, histamine-rabbit serum albumin-Sepharose; KLH, keyhole limpet hemocyanin; Pi/NaCl, phosphate-buffered saline. 2405The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

Regulation of Immune Response by Preadministration of Cells Briefly Pulsed with Antigen in vitro

“…In general the targets of Ts are thought to be helper T cell [18] or B cell [19], but some investigators suggest that macrophages are also targets of Ts [7,8]. Accord ing to the results obtained in figures 3 and 5, we show that Ts induces the reduction of antigen presenting activity of SACs, in other words, SACs are one of the targets ofTs.…”

“…The importance of antigen presenting cells in the initiation of immune responses is widely acknowledged [4][5][6]. Some investi gators have demonstrated that antigen presentation by macrophages is reduced in immunologically toler ant animals [7,8], Antigen presenting cells in tolerant animals is not, however, thoroughly studied.…”

T lymphocytes specific for immunoglobulin allotype. I. Igh- 1(b)-specific T cells demonstrated by suppression in vivo and cytotoxicity in vitro

“…Another precedent for the suggestion that Tc may regulate expression of Ig in vivo is the demonstration of Segal et al (33) that T cells from high zone tolerant mice could kill macrophages pulsed with the tolerizing antigen . However, Abbas et al (34)(35)(36) have shown recently that suppression and cytotoxicity may operate by quite different mechanisms at the level of the target cell .…”

Correlation between perchloric‐acid‐soluble serum proteins, cellular immunity and tumor‐cell burden

“…These factors inhibit the generation of PFC activity following immunization with sheep erythrocates. A high dose of R3230 AdCa-associated antigen may also induce suppressor cells from tolerant cells which inactivate antigen presenting macrophages, leading to a decline in the host cell-mediated immunity (Segal et al, 1979).…”