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Intravenous Injection of Soluble Antigen Induces Thymic and Peripheral T-Cell Apoptosis
Roland S. Liblau, Roland Tisch, Kevan Shokat, Xiao-Dong Yang, Nicole Dumont, Christopher C. Goodnow and Hugh O. McDevitt
Proceedings of the National Academy of Sciences of the United States of America
Vol. 93, No. 7 (Apr. 2, 1996), pp. 3031-3036
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/39110
Page Count: 6
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The mechanism by which tolerance is induced via systemic administration of high doses of aqueous antigen has been analyzed by using mice transgenic for a T-cell receptor specific for the influenza virus hemagglutinin (HA) peptide comprising amino acids 126-138. After intravenous injection of 750 (but not 75) μ g of HA peptide, a state of hyporesponsiveness was rapidly induced. In the thymus, in situ apoptosis in the cortex and at the corticomedullary junction was responsible for a synchronous and massive deletion of CD4+ CD8+ thymocytes. In secondary lymphoid organs, HA-reactive T cells were initially activated but were hyporesponsive at the single cell level. After 3 days, however, those cells were rapidly deleted, at least partially, through an apoptotic process. Therefore, both thymic and peripheral apoptosis, in addition to T-cell receptor desensitization, contribute to high-dose tolerance.
Proceedings of the National Academy of Sciences of the United States of America © 1996 National Academy of Sciences