Related Experiment Videos
CD4+ T cells require adhesion via LFA-1/ICAM-1 to induce target apoptosis in TNF-independent pathway
1Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Abstract:
An antigen-specific CD4+ T cell clone, OK2.21, and a hybridoma clone, A3.4C6, induced cytolysis and DNA fragmentation of appropriate targets in the presence of an anti-CD3 monoclonal antibody (Mab). In a double chamber system, OK2.21 killed TNF-sensitive targets that were separated from the T cells by a porous membrane. The killing was completely inhibited by anti-TNF antibody. On the other hand, neither OK2.21 nor A3.4C6 killed a TNF-insensitive target, A20.2J, that was separated from the T cells. Furthermore, the cytotoxicity and DNA fragmentation of A20.2J by anti-CD3 Mab-activated T cells were inhibited by both anti-LFA-1 and anti-ICAM-1 Mab. These results suggest that TNF is the only soluble cytolytic factor involved in CD4+ T cell-mediated cytotoxicity, and that TNF-independent apoptosis occurs through cell-to-cell contact via a LFA-1/ICAM-1 system.
Insights
Tumor necrosis factor (TNF) is the sole soluble factor mediating CD4+ T cell cytotoxicity. TNF-independent apoptosis involves cell-to-cell contact through the LFA-1/ICAM-1 pathway, highlighting distinct mechanisms in T cell-mediated killing.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD4+ T cells play a crucial role in immune responses, including target cell killing.
- Mechanisms of T cell-mediated cytotoxicity involve soluble factors and direct cell contact.
Purpose of the Study:
- To elucidate the specific mechanisms of CD4+ T cell-mediated cytotoxicity.
- To differentiate between TNF-dependent and TNF-independent apoptotic pathways.
Main Methods:
- Utilized antigen-specific CD4+ T cell clones (OK2.21) and hybridoma clones (A3.4C6).
- Employed a double-chamber system to separate effector T cells from target cells.
- Assessed cytolysis and DNA fragmentation in the presence of anti-CD3 monoclonal antibody (Mab).
- Investigated the role of TNF, LFA-1, and ICAM-1 using specific blocking antibodies.
Main Results:
- OK2.21 killed TNF-sensitive targets separated by a membrane, an effect inhibited by anti-TNF antibody.
- Neither T cell clone killed TNF-insensitive targets (A20.2J) when separated.
- Cytotoxicity against A20.2J by anti-CD3 Mab-activated T cells was inhibited by anti-LFA-1 and anti-ICAM-1 antibodies.
Conclusions:
- TNF is the exclusive soluble mediator of CD4+ T cell-induced cytotoxicity.
- TNF-independent apoptosis is mediated by cell-to-cell contact, involving the LFA-1/ICAM-1 interaction system.