Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity

AUTOR(ES)

Salmena, Leonardo

FONTE

Cold Spring Harbor Laboratory Press

RESUMO

Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We generated mice with a targeted caspase 8 mutation that is restricted to the T-cell lineage. Despite normal thymocyte development in the absence of caspase 8, we observed a marked decrease in the number of peripheral T-cells and impaired T-cell response ex vivo to activation stimuli. caspase 8 ablation protected thymocytes and activated T-cells from CD95 ligand but not anti-CD3-induced apoptosis, or apoptosis activated by agents that are known to act through the mitochondria. caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. These findings identify an essential, cell-stage-specific role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. This is consistent with the recent identification of caspase 8 mutations in human immunodeficiency.

Documentos Relacionados

• T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destruction
• T-cell-mediated cytotoxicity against autologous malignant melanoma: analysis with interleukin 2-dependent T-cell cultures.
• T-cell-mediated immunity in persistent Mycobacterium intracellulare infections in mice.
• Role of Macrophage Inflammatory Protein-1α in T-Cell-Mediated Immunity to Viral Infection
• Regulation and Function of T-Cell-Mediated Immunity during Toxoplasma gondii Infection