Apoptosis-induced inhibition of CD1d-mediated antigen presentation: different roles for caspases and signal transduction pathways
Graduate School of Biomedical Sciences; Department of Microbiology and Immunology
Medical Subject Headings
Animals; Antigen Presentation; Antigens, CD1; Antigens, CD1d; Apoptosis; Camptothecin; Caspases; Cells, Cultured; Ceramides; Coculture Techniques; Female; Galactosylceramides; Meperidine; Mice; Mice, Inbred C57BL; Protein Kinase C-delta; Signal Transduction; p38 Mitogen-Activated Protein Kinases
Life Sciences | Medicine and Health Sciences
The stimulation of programmed cell death can either enhance or inhibit antigen presentation by classic major histocompatibility complex molecules. In the current study, we report that the induction of apoptosis by topoisomerase I inhibition or elevation of intracellular ceramide levels substantially impairs CD1d-mediated antigen presentation. In the former case, such a reduction occurred via the regulation of both the p38 mitogen-activated protein kinases and protein kinase C delta signal transduction pathways as well as the caspase cascade, whereas the latter was p38-(but not caspase)-dependent. Confocal microscopic analysis showed an altered intracellular distribution of CD1d following the inhibition topoisomerase I or by an increase in intracellular ceramide levels, that was prevented by p38 and caspase inhibitors. Thus, the induction of apoptosis in antigen presenting cells severely compromises CD1d-mediated antigen presentation by multiple mechanisms.
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Citation: Immunology. 2008 Sep;125(1):80-90. Epub 2008 Mar 14. Link to article on publisher's site
Khan, Masood A.; Sriram, Venkataraman; Renukaradhya, Gourapura J.; Du, Wenjun; Gervay-Hague, Jacquelyn; and Brutkiewicz, Randy R., "Apoptosis-induced inhibition of CD1d-mediated antigen presentation: different roles for caspases and signal transduction pathways" (2008). GSBS Student Publications. 1466.