Cytotoxic mechanisms employed by mouse T cells to destroy pancreatic β-cells.

ABSTRACT: Several cytotoxic mechanisms have been attributed to T cells participating in β-cell death in type 1 diabetes. However, sensitivity of β-cells to these mechanisms in vitro and in vivo is likely to be different. Moreover, CD4⁺ and CD8⁺ T cells may use distinct mechanisms to cause β-cell demise that possibly involve activation of third-party cytotoxic cells. We used the transfer of genetically modified diabetogenic T cells into normal, mutant, and bone marrow chimeric recipients to test the contribution of major cytotoxic mechanisms in β-cell death. We found that 1) the killing of β-cells by CD4⁺ T cells required activation of the recipient's own cytotoxic cells via tumor necrosis factor-α (TNF-α); 2) CD8⁺ T-cell cytotoxic mechanisms destroying β-cells were limited to perforin and Fas ligand

SUBMITTER: Varanasi V 

PROVIDER: S-EPMC3478530 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature