Intravenous injection of soluble antigen induces thymic and peripheral T-cells apoptosis.
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.
Liblau
R S
RS
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305, USA.
Tisch
R
R
Shokat
K
K
Yang
X
X
Dumont
N
N
Goodnow
C C
CC
McDevitt
H O
HO
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D007108:Immune Tolerance; D007275:Injections, Intravenous; D008198:Lymph Nodes / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology*
D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin