Intravenous injection of soluble antigen induces thymic and peripheral T-cells apoptosis.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Intravenous injection of soluble antigen induces thymic and peripheral T-cells apoptosis.

Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3031-6. Unique Identifier : AIDSLINE MED/96181528
Liblau RS; Tisch R; Shokat K; Yang X; Dumont N; Goodnow CC; McDevitt HO; Department of Microbiology and Immunology, Stanford University; School of Medicine, CA 94305, USA.

Abstract: 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) micrograms 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.

Keywords: Amino Acid Sequence Animal Antigens, Viral/ADMINISTRATION & DOSAGE/*IMMUNOLOGY/PHARMACOLOGY *Apoptosis/DRUG EFFECTS CD4-Positive T-Lymphocytes/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Flow Cytometry Hemagglutinins, Viral/ADMINISTRATION & DOSAGE/*IMMUNOLOGY/ PHARMACOLOGY Immune Tolerance Injections, Intravenous Lymph Nodes/IMMUNOLOGY Lymphocyte Depletion Mice Mice, Transgenic Molecular Sequence Data Ovalbumin/ADMINISTRATION & DOSAGE/IMMUNOLOGY/PHARMACOLOGY Peptide Fragments/ADMINISTRATION & DOSAGE/IMMUNOLOGY/PHARMACOLOGY Receptors, Antigen, T-Cell, alpha-beta/*BIOSYNTHESIS/GENETICS Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes/DRUG EFFECTS/*IMMUNOLOGY/PHYSIOLOGY Thymectomy Thymus Gland/*IMMUNOLOGY JOURNAL ARTICLE
960830
M9681146

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