Induction of Immunological Tolerance to a Thymus-Dependent Antigen in the Absence of Thymus-Derived Cells

The ability of colchicine (Col) to interfere with suppressor cells specific for the soluble protein antigen human gamma globulin (HGG) has been examined. This interference may be the mechanism of the adjuvanticity promoted by Col. When injected into A/J mice at the appropriate time and concentration, both Col and cyclophosphamide promoted an adjuvant increase in the plaque-forming cell response to 100 micrograms of immunogenic, aggregated HGG. Col abrogated both the induction of suppressor cells when injected with 3 h of tolerization with deaggregated (DHGG) and the expression of previously induced suppressor cells when injected with the antigenic challenge. Interference with the generation and expression of antigen-specific suppressor cells had no detectable effects on the immunologic unresponsive state to HGG. Col did not interfere with the induction of tolerance at a dose (1 mg/kg) that abolished the generation of suppressor cells. Furthermore, the absence of colchicine-sensitive-suppressor cells during the establishment of tolerance had no observable effect on the duration of unresponsivness in either helper T- or B-lymphocyte populations. Finally, Col was not able to terminate the unresponsive state established by DHGG even when responsive splenic B cells could be demonstrated in tolerant animals. These data indicate that suppressor cells are not required for the establishment and maintenance of the unresponsive state to this antigen.

Section: Inability Of Col Tosupporting

confidence: 49%

Section: Inability Of Col Tomentioning

confidence: 97%

mentioning

confidence: 99%

See 1 more Smart Citation

Induction and mode of action of suppressor cells generated against human gamma globulin. II. Effects of colchicine.

Parks¹,

Shaller²,

Weigle³

1979

“…Additionally, the mechanism is likely to differ in the case of thymus-dependent and thymus-independent antigens since the latter substances in fact nonspecifically abrogate B-cell tolerance induction by the former (7,8). Questions particularly suited to an in vitro analysis of tolerance induction in splenic B cells concern the proposal of Diener and Feldmann (9) that a multivalent presentation of antigen is an obligatory requirement for tolerance induction in the B cell, and also the kinetics of tolerance induction in a defined pool of B cells that is not being altered by the B-cell neogenesis that occurs in the bone marrow (10) .…”

mentioning

confidence: 99%

The in vitro induction of immunological tolerance in the B lymphocyte by oligovalent thymus-dependent antigens.

Schrader¹

1975

B-cell tolerance has been induced by oligovalent thymus-dependent antigens in an entirely in vitro system. Dissociated spleen cells from congenitally athymic (nu/nu) mice were preincubated for 24 h with 0.1 -- 1 mg/ml of either fowl gamma globulin (FGG) of DNP-human gamma globulin (DNP-HGG). After washing, the cells were tested for the ability to mount in vitro, thymus-independent responses against FGG and DNP. A state of specific responsiveness to either FGG or DNP was thus demonstrated. Features of this wholly in vitro system that paralleled previous findings on the in vivo induction of B-cell tolerance in nu/nu mice were the kinetics, 24 h being required for tolerance induction in either case, the abrogation of tolerance induction by the presence of POL both in vivo and in vitro, and finally the observation that in neither case was there a requirement for the antigens to be deaggregated. It was shown that DNP-(Fab) 2 fragments prepared from HGG induced DNP-specific tolerance indicating that the Fc piece was not required for tolerance induction in this in vitro system. DNP-bovine serum albumin was less effective than DNP-HGG or DNP-(Fab)2. Preincubation with subtoxic concentrations of DNP-lysine of DNP-epsilon-capric acid had only a marginal effect on DNP responsiveness. Since nu/nu mice, lacking in detectable T-cell function, were used as spleen cell donors, this work provides further evidence that B-cell tolerance to thymus-dependent antigens can be induced without the participation of T cells. It is suggested that B-cell tolerance to thymus-dependent antigens occurs when the antigen in a sufficient concentration and over a sufficient period of time has direct access to the B cell. This contact with antigen must be in the absence of an additional influence provided either by adjuvants like endotoxin or POL, or by activated macrophages, which may be stimulated by activated T cells; otherwise not tolerance but B-cell activation will occur.

“…While it is clearly possible to induce Bcell tolerance in the absence of T lymphocytes (23)(24)(25), some workers have suggested that the presence of T cells tends to protect B lymphocytes from tolerance induction (26)(27)(28)(29)(30). In the present studies it is apparent that B-cell tolerance can be induced in reconstituted mice which were thymic deficient.…”

Section: Restoration Of a "Normal" Response To Tolerance Induction Inmentioning

confidence: 99%

Differences in the mechanism of tolerance to dinitrophenylated bovine gamma globulin when induced in normal adult mice or in reconstituted irradiated mice: dependence of the mechanism of tolerance on the structural organization of the lymphoid system.

Szewczuk¹,

Halliday²,

Soybel³

et al. 1977

In recent years it has become apparent that a variety of distinct mechanisms can lead to a state of specific immunologic tolerance. Clonal deletion of T and/or B lymphocytes (1), activation of specific suppressor T lymphocytes (2), and the production of small amounts of high affinity antibody (3) are among the well-defined mechanisms of immunologic unresponsiveness. At least two types of B-lymphocyte tolerance (reversible and irreversible) plus peripheral neutralization of antibody Ctreadmill hypothesis") have been definitively shown to operate in tolerance to T-independent antigens (4). In addition, recent studies have suggested that the interaction of antigen with antibodyproducing B lymphocytes can lead to a decrease in the rate of antibody secretion (effector cell blockade) (5) and that anti-idiotype antibody might be capable of mediating tolerance (6). Other than the observations of Weigle et al. (1) that higher doses of antigen are required for tolerance induction in B lymphocytes than in T lymphocytes, relatively little is known as to what factors determine which mechanism will be operative in any given unresponsive state.