DBA/2 mice are highly susceptible while BALB/c mice are resistant to the induction of tolerance with ultracentrifuged BGG. As measured by the clearance of a test dose of 125-I-BGG, 2 mg ...ultracentrifuged BGG is sufficient to induce complete tolerance in DBA/2 mice, while BALB/c mice exhibit a clearance rate similar to immune controls. BALB/c mice pretreated with carrageenan (a macrophage toxic agent) lose their resistance to tolerance induction with 2 mg ultracentrifuged BGG, while treatment with cobra venom factor does not alter their resistance to tolerance induction. Stimulation of the reticuloendothelial system with BCG produces a reduction in the susceptibility to tolerance of DBA/2 mice. This effect is transitory, with the maximum effect 3 weeks after BCG infection. Biologic filtration of BGG through BALB/c mice results in a preparation which is highly tolerogenic for recipient mice and this ability to filter the immunogenic portion of BGG is radioresistant. The results provide evidence for the concept that the differential susceptibility to the induction of tolerance is related to a macrophage function in the inductive phase of immunity.
Dark August rats exhibit clinically and histologically verified experimental allergic encephalomyelitis (EAE) when immunized with appropriate antigen (nervous tissue, myelin basic protein) emulsified ...in complete Freund's adjuvant (CFA). We provide evidence that 6,6'-trechalose dymicolate (TDM) incorporated in incomplete Freund's adjuvant replaces CFA in EAE induction. The animals that recovered from EAE were resistant to the reinduction of the disease irrespectively whether Mycobacterium tuberculosis or TDM was used as an adjuvant. Finally, pretreatment with CFA alone was sufficient for prevention of disease elicited by challenge with encephalitogen + CFA. However, TDM, despite its adjuvant capacity when applied prior to the induction of the disease with encephalitogen + CFA, did not exhibit any protective effect. Thus, our study implicates that adjuvant and suppressive capacities of M. tuberculosis may be related to the different determinants of the microorganisms, TDM possessing the adjuvanticity only.
Accessory cell function of mouse and human epidermal cells (ECs) was analyzed by measuring their capacity to support the proliferative response of lectin-stimulated nonadherent thymic T cells (NATs). ...NATs exhibit low responsiveness to lectins, while the addition of ECs induced in a dose-dependent way either supportive or suppressive effects. Accessory function of ECs was not genetically restricted and could be partially replaced by soluble products of ECs. In vitro X-irradiation with 3000 R increased rather than impaired helper effects of ECs. In vitro exposure of ECs to hydrocortisone inhibits the production of stimulatory EC-derived factors and favor the production of factor(s) which suppress NAT proliferation. Additionally, ECs obtained from mouse skin to which glucocorticoids were topically applied, produced factor(s) which inhibited lectin-induced proliferation of NATs. Thus, it appears that immunosuppressive effects of topically applied glucocorticoids may partially be due to the abolition of the production of the factor(s) which stimulate cell proliferation within skin and/or to the enhancement of the activity of suppressive factor(s).