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- W2100585903 abstract "Granulysin is located in the acidic granules of cytotoxic T cells. Although the purified protein has antimicrobial activity against a broad spectrum of microbial pathogens, direct evidence for granulysin-mediated cytotoxicity has heretofore been lacking. Studies were performed to examine the regulation and activity of granulysin expressed by CD8 T cells using Cryptococcus neoformans, which is one of the most common opportunistic pathogens of AIDS patients. IL-15-activated CD8 T cells acquired anticryptococcal activity, which correlated with the up-regulation of granulysin. When granules containing granulysin were depleted using SrCl(2,) or when the gene was silenced using 21-nt small interfering RNA duplexes, the antifungal effect of CD8 T cells was abrogated. Concanamycin A and EGTA did not affect the antifungal effect, suggesting that the activity of granulysin was perforin independent. Following stimulation by the C. neoformans mitogen, CD8 T cells expressed granulysin and acquired antifungal activity. This activity required CD4 T cells and was dependent upon accessory cells. Furthermore, IL-15 was both necessary and sufficient for granulysin up-regulation in CD8 T cells. These observations are most consistent with a mechanism whereby C. neoformans mitogen is presented to CD4 T cells, which in turn activate accessory cells. The resultant IL-15 activates CD8 T cells to express granulysin, which is responsible for antifungal activity." @default.
- W2100585903 created "2016-06-24" @default.
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- W2100585903 creator A5091074676 @default.
- W2100585903 date "2002-11-15" @default.
- W2100585903 modified "2023-09-25" @default.
- W2100585903 title "CD8 T Cell-Mediated Killing of<i>Cryptococcus neoformans</i>Requires Granulysin and Is Dependent on CD4 T Cells and IL-15" @default.
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- W2100585903 doi "https://doi.org/10.4049/jimmunol.169.10.5787" @default.
- W2100585903 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12421959" @default.
- W2100585903 hasPublicationYear "2002" @default.
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