INTRAVENOUS-INJECTION OF SOLUBLE-ANTIGEN INDUCES THYMIC AND PERIPHERAL T-CELL APOPTOSIS

The mechanism by which tolerance is induced via systemic administratio n of high doses of aqueous antigen has been analyzed by using mice tra nsgenic for a T-cell receptor specific for the influenza virus hemaggl utinin (HA) peptide comprising amino acids 126-138, After intravenous injection of 750 (but not 75) mu g of HA peptide, a state of hyporespo nsiveness was rapidly induced, In the thymus, in situ apoptosis in the cortex and at the corticomedullary junction was responsible for a syn chronous and massive deletion of CD4(+) CD8(+) thymocytes, In secondar y lymphoid organs, HA-reactive T cells were initially activated but we re hyporesponsive at the single cell level, After 3 days, however, tho se cells were rapidly deleted, at least partially, through an apoptoti c process, Therefore, both thymic and peripheral apoptosis, in additio n to T-cell receptor desensitization, contribute to high-dose toleranc e.