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rdf:type |
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lifeskim:mentions |
umls-concept:C0010416,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0162388,
umls-concept:C0254610,
umls-concept:C0851827,
umls-concept:C1332714,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1415164,
umls-concept:C1546857,
umls-concept:C1701901,
umls-concept:C1706438,
umls-concept:C2698600
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pubmed:issue |
10
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pubmed:dateCreated |
2002-11-7
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antifungal Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/GNLY protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-15,
http://linkedlifedata.com/resource/pubmed/chemical/Macrolides,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/Perforin,
http://linkedlifedata.com/resource/pubmed/chemical/Pore Forming Cytotoxic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/concanamycin A
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
169
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5787-95
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pubmed:dateRevised |
2010-9-1
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pubmed:meshHeading |
pubmed-meshheading:12421959-Adjuvants, Immunologic,
pubmed-meshheading:12421959-Adult,
pubmed-meshheading:12421959-Anti-Bacterial Agents,
pubmed-meshheading:12421959-Antifungal Agents,
pubmed-meshheading:12421959-Antigens, Differentiation, T-Lymphocyte,
pubmed-meshheading:12421959-CD4-Positive T-Lymphocytes,
pubmed-meshheading:12421959-CD8-Positive T-Lymphocytes,
pubmed-meshheading:12421959-Cell Separation,
pubmed-meshheading:12421959-Cryptococcus neoformans,
pubmed-meshheading:12421959-Cytotoxicity, Immunologic,
pubmed-meshheading:12421959-Humans,
pubmed-meshheading:12421959-Interleukin-15,
pubmed-meshheading:12421959-Leukocytes, Mononuclear,
pubmed-meshheading:12421959-Lymphocyte Activation,
pubmed-meshheading:12421959-Macrolides,
pubmed-meshheading:12421959-Membrane Glycoproteins,
pubmed-meshheading:12421959-Mitogens,
pubmed-meshheading:12421959-Perforin,
pubmed-meshheading:12421959-Pore Forming Cytotoxic Proteins,
pubmed-meshheading:12421959-Up-Regulation
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pubmed:year |
2002
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pubmed:articleTitle |
CD8 T cell-mediated killing of Cryptococcus neoformans requires granulysin and is dependent on CD4 T cells and IL-15.
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pubmed:affiliation |
Department of Medical Sciences, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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