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From the Department of Immunology Research, Roswell Park Memorial Institute,2 666 Elm Street, Buffalo, New York 14263
Abstract
The bacterial dextran B1355, which is normally a potent thymus-independent immunogen, was made tolerogenic by oxidation. The injection of the oxidized dextran into BALB/c mice before, at the same time, or up to 4 days after the injection of the immunogenic form of the dextran resulted in a marked immunologically specific suppression of the number of anti-dextran antibody-forming cells found in the spleen. This suppression resulted from a direct inactivation of antibody-forming cell precursors rather than from either inhibition of antibody secretion or the exhaustive utilization of precursor B cells that have been observed in other tolerance systems. A substantial degree of tolerance was achieved after only a 1-hr in vivo exposure of the spleen cells to the tolerogen. At a dose of 1 mg of oxidized dextran per mouse, tolerance persisted for at least 3 weeks. A complete recovery was apparent by 10 weeks. The stability of the tolerance was demonstrated by transferring tolerant spleen cells to irradiated recipients. The response in the recipient animals to an immunogenic dextran challenge remained suppressed. It appears that the tolerogenicity of the oxidized dextran is due to its ability to couple covalently with free amino groups in or near the receptor site of the cell membrane via the reactive dialdehyde groups of the dextran.
Footnotes
1 This investigation was supported in part by Grants AI-03962, awarded by the National Institute of Allergy and Infectious Diseases, P30-17609, awarded by the National Cancer Institute, both of the Department of Health, Education and Welfare, and by Institutional Research Grant IN-54-P-1 awarded by the American by the American Cancer Society.
2 A unit of the New York State Department of Health.
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