The suppressive effect of thymus cells on the agglutinating antibody response in chickens is shown to be antigen‐specific. Experiments reveal that this effect can be seen several weeks after thymus cell transfer, if the respective antigen (A) is given 3 times weekly after transfer. Repeatedly applied high doses of the antigen (A) result in a stronger effect than low antigen doses, and mercaptoethanol‐resistant antibody (IgG) is usually more affected than the total titer (of which IgM is the major contributor). Finally, several weeks after thymus cell transfer, when the response to antigen A is still lower than that of the normal controls, the antibody response to an unrelated antigen B is normal. By these three criteria, as well as by the degree of suppression, the suppressive effect of thymus cells strikingly resembles the phenomenon of antigen‐specific suppression that is seen after antigenic stimulus in the prenatal or early postnatal period.
The suppressive effect is already given by thymus cells from 10‐day old donors. As in previous studies, the suppressive activity was significantly diminished in thymus cells from neonatally bursectomized donors. The data indicate that a specifically acting suppressor cell compartment exists which is different from B cells and cooperative or graft‐vs‐host‐active T cells.
The results are discussed in light of current concepts of “self‐tolerance”.
Bone marrow-derived macrophages (BMM phi) were shown before to function as antigen-presenting cells. We show here, that the antigen presentation capacity of BMM phi depends on the nature of the antigen and is differently regulated by the lymphokines interferon-gamma (IFN-gamma) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). When bovine insulin (BI) was employed as antigen, only BMM phi treated with GM-CSF (GM-CSF-M phi) were efficient presenters, but when presentation of the antigens ovalbumin and conalbumin was tested, IFN-gamma-pulsed BMM phi (IFN-gamma-M phi) proved superior to GM-CSF-M phi. The lack of efficient BI presentation function of IFN-gamma-M phi was only obvious, when native BI was used as antigen. Preprocessed BI was presented by IFN-gamma-M phi with drastically higher efficiency than by GM-CSF-M phi. Because processing of insulin depends on reduction of disulfide bonds, we analyzed the content of intracellular reducing thiols within IFN-gamma-M phi, GM-CSF-M phi, and untreated BMM phi. Only after stimulation with GM-CSF did the amount of reduced glutathione and cysteine strongly increase, while IFN-gamma did not efficiently augment the intracellular content of both thiols. These findings suggest that the lymphokines IFN-gamma and GM-CSF differently interfere with the processing capacity of BMM phi by differently regulating the intracellular concentration of the thiols reduced glutathione and cysteine. A high level of these thiols induced by GM-CSF correlates with a prominent capacity to present the antigen bovine insulin.
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