The involvement of T-suppressor cells in hapten-modified self unresponsiveness induced in vivo is well established. However, TNP-modified syngeneic spleen cells (TNP-SC) can block the anti-TNP PFC response of normal or nude spleen cells to TNP-immunogen in vitro, an effect that is apparently T cell-independent. In this study, we have used a 2-stage culture system in which both the induction of tolerance by irradiated syngeneic TNP-SC and the subsequent challenge with TNP-immunogen take place in vitro to dissect the cellular events that lead to unresponsiveness. Our results show that not only are spleen cells precultured with TNP-SC tolerant to challenge, but that these cells are able to specifically suppress the response of freshly prepared normal spleen cells to the T-independent antigens TNP-POL or TNP-LPS. Irradiation of the precultured cells abrogates the suppressor activity and rules out hapten carryover as the mechanism of suppression. Suppressor cells were able to inhibit the response of anti-Ba theta and C-treated spleen cells, suggesting that suppressor function is directed toward the B cell and/or accessory cells. Anti-Ba theta and C treatment of spleen cells before preculture with TNP-SC prevented the induction of both tolerance and suppression. Nylon wool-enriched T cells, on the other hand, could generate suppressor cells in response to TNP-SC. These results demonstrate that, like the in vivo situation, T cells are involved in the generation of this form of B cell tolerance in vitro. Implications relevant to the mechanisms of tolerance induction are discussed.

Animals↗

PubMed1980

Role of self carriers in the immune response and tolerance. VII. Importance of H-2 antigens in the in vitro induction of tolerance and suppression to hapten-modified self.

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Animals↗

PubMedDate not supplied

Chemical modification of surface active poly(ethylene oxide)-poly (propylene oxide) triblock copolymers.

A general route has been developed to chemically modify a series of poly(ethylene oxide)-poly(propylene oxide) triblock copolymers with molecular weights from 6500 to 14600. It is initiated by the introduction of p-nitrophenyl groups; such nitrophenyl conjugated copolymers are stable in an organic milieu and in a dry state but are seen to react easily with amino-containing molecules including small peptides. Among them, introduction of 2-pyridyl disulfide groups after coupling with 2-(2-pyridyldithio)ethylamine enables the selective attachment of thiol-containing molecules. The released thiopyridone in such thiol-disulfide reactions can be used to quantify the content of 2-pyridyl disulfide groups. In addition, a new type of modified copolymers was developed for the radioisotope (125I) labeling purpose that consists of a reaction of nitrophenyl conjugated copolymers with hydrazine and a subsequent coupling with N-succinimidyl 3-(4-hydroxyphenyl)propionate (Bolton-Hunter reagent). Adsorption studies of 125I-labeled and 2-pyridyl disulfide conjugated copolymers on polystyrene particles are consistent with previous determinations of surface coverage using other technologies, in turn indicating that this new chemical modification does not alter their surfactant properties on hydrophobic solid phase. The coating of common hydrophobic surfaces with 2-pyridyl disulfide conjugated copolymers has been demonstrated as a general and robust immobilization method to generate a high-sensitivity bioactive surface with low nonspecific binding. The optimal space between immobilized ligands can also be controlled by incubating the solid phase with solutions containing mixtures with different ratios of unmodified and modified copolymers.

Chemical Phenomena↗