Induction by Antigen of Intrathymic Apoptosis of CD4 ⁺ CD8 ⁺ TCR ^lo Thymocytes in Vivo

TLDR

Transgenic mice expressing a TCR specific for the peptide contain thymocytes that mature from immature to mature phenotypes. The study aimed to investigate the mechanisms of clonal deletion of autoreactive T cells by inducing deletion with a peptide antigen in vivo. A peptide antigen was administered intraperitoneally to trigger deletion of antigen‑reactive thymocytes in vivo. Intraperitoneal peptide administration caused rapid deletion of immature CD4⁺CD8⁺ TCR^lo thymocytes, with apoptosis evident within 20 h, providing direct evidence that apoptosis drives antigen‑induced tolerance.

Abstract

In order to examine the mechanisms by which clonal deletion of autoreactive T cells occurs, a peptide antigen was used to induce deletion of antigen-reactive thymocytes in vivo. Mice transgenic for a T cell receptor (TCR) that reacts to this peptide contain thymocytes that progress from the immature to the mature phenotype. Intraperitoneal administration of the peptide antigen to transgenic mice results in a rapid deletion of the immature CD4 + CD8 + TCR lo thymocytes. Apoptosis of cortical thymocytes can be seen within 20 hours of treatment. These results provide direct evidence for the in vivo role of apoptosis in the development of antigen-induced tolerance.