Related Experiment Videos
The liver eliminates T cells undergoing antigen-triggered apoptosis in vivo
L Huang1, G Soldevila, M Leeker
1Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Abstract:
Deletion of mature peripheral T cells may result from TCR ligation by bacterial enterotoxins, endogenous provirus-encoded superantigens, and peptide antigens. But the ultimate fate of deleted T cells is not clear. Using a line of T cell receptor transgenic mice injected with antigenic peptide, we have documented that peripheral deletion is accompanied by the induction of abortive T cell activation followed by the disappearance of transgene-positive T cells. As these T cells disappear from the lymph nodes and spleen, they accumulate in the liver, where they undergo apoptosis. This is likely to be a general clearance pathway for T cells that are programmed to undergo apoptosis in vivo, and it may further explain the expansion of the intrahepatic T cell pool in mice with genetic defects in the T cell apoptosis mechanism, such as the lpr mutant.
Insights
Peripheral T cells deleted via TCR ligation accumulate in the liver, undergoing apoptosis. This study reveals a novel clearance pathway for T cells programmed for deletion in vivo.
Area of Science:
- Immunology
- Cell Biology
Background:
- Mature peripheral T cells can be deleted through various mechanisms, including T cell receptor (TCR) ligation by superantigens or peptide antigens.
- The ultimate fate and clearance pathway of these deleted T cells remain unclear.
Purpose of the Study:
- To investigate the in vivo fate of T cells undergoing peripheral deletion.
- To elucidate the clearance mechanism for T cells programmed for apoptosis.
Main Methods:
- Utilized T cell receptor transgenic mice.
- Administered antigenic peptide to induce T cell deletion.
- Tracked the distribution and fate of T cells in lymphoid organs and the liver.
Main Results:
- Peripheral deletion of T cells is preceded by abortive T cell activation.
- Deleted T cells disappear from lymph nodes and spleen.
- Accumulation of deleted T cells in the liver, where they undergo apoptosis.
Conclusions:
- Peripheral T cell deletion involves an abortive activation phase followed by apoptosis.
- The liver serves as a significant site for the clearance of deleted T cells via apoptosis.
- This pathway may explain intrahepatic T cell expansion in mice with apoptosis defects.