| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
* Medical Sciences and
Microbiology and Infectious Disease and Internal Medicine, University of Calgary, Calgary, Alberta, Canada; and
Department of Pediatrics, Stanford University, Stanford, CA 94305
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 SrCl2, 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.
This article has been cited by other articles:
|
|
 |
|
  T. A. Smith-Norowitz, J. Silverberg, K. B. Norowitz, M. H. Bluth, S. Chice, R. Joks, M. Nowakowski, and H. G. Durkin Two Distinct T Cell Subsets, CD4+ and CD8+CD60+, and Their Cytokines Are Required for In Vitro Induction of Human Ragweed-Specific Memory IgE Responses J. Immunol., October 1, 2008; 181(7): 4761 - 4769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nakashima, A. Shiozaki, S. Myojo, M. Ito, M. Tatematsu, M. Sakai, Y. Takamori, K. Ogawa, K. Nagata, and S. Saito Granulysin Produced by Uterine Natural Killer Cells Induces Apoptosis of Extravillous Trophoblasts in Spontaneous Abortion Am. J. Pathol., September 1, 2008; 173(3): 653 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. G. da Silva, D. Unks, S.-c. Lyu, J. Ma, R. Zbozien-Pacamaj, X. Chen, A. M. Krensky, and C. Clayberger In vitro and in vivo antimicrobial activity of granulysin-derived peptides against Vibrio cholerae J. Antimicrob. Chemother., May 1, 2008; 61(5): 1103 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Muller, W. Stenzel, G. Kohler, C. Werner, T. Polte, G. Hansen, N. Schutze, R. K. Straubinger, M. Blessing, A. N. J. McKenzie, et al. IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans J. Immunol., October 15, 2007; 179(8): 5367 - 5377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. D. Wiseman, L. L. Ma, K. J. Marr, G. J. Jones, and C. H. Mody Perforin-Dependent Cryptococcal Microbicidal Activity in NK Cells Requires PI3K-Dependent ERK1/2 Signaling J. Immunol., May 15, 2007; 178(10): 6456 - 6464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. F. Zheng, L. L. Ma, G. J. Jones, M. J. Gill, A. M. Krensky, P. Kubes, and C. H. Mody Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and activation of this pathway is defective in HIV patients Blood, March 1, 2007; 109(5): 2049 - 2057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Huang, S.-C. Lyu, C. Clayberger, and A. M. Krensky Granulysin-Mediated Tumor Rejection in Transgenic Mice J. Immunol., January 1, 2007; 178(1): 77 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Liu, S. Liu, X. Qu, and J. Liu Construction of a eukaryotic expression system for granulysin and its protective effect in mice infected with Mycobacterium tuberculosis. J. Med. Microbiol., October 1, 2006; 55(Pt 10): 1389 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Siddiqui, R. J. Shattock, and T. S. Harrison Role of Capsule and Interleukin-6 in Long-Term Immune Control of Cryptococcus neoformans Infection by Specifically Activated Human Peripheral Blood Mononuclear Cells Infect. Immun., September 1, 2006; 74(9): 5302 - 5310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Zhou, R. A. Gault, T. R. Kozel, and W. J. Murphy Immunomodulation with CD40 Stimulation and Interleukin-2 Protects Mice from Disseminated Cryptococcosis Infect. Immun., April 1, 2006; 74(4): 2161 - 2168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. McAllister, C. Steele, M. Zheng, J. E. Shellito, and J. K. Kolls In Vitro Effector Activity of Pneumocystis murina-Specific T-Cytotoxic-1 CD8+ T Cells: Role of Granulocyte-Macrophage Colony-Stimulating Factor Infect. Immun., November 1, 2005; 73(11): 7450 - 7457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Ma, C. L. C. Wang, G. G. Neely, S. Epelman, A. M. Krensky, and C. H. Mody NK Cells Use Perforin Rather than Granulysin for Anticryptococcal Activity J. Immunol., September 1, 2004; 173(5): 3357 - 3365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Endsley, J. L. Furrer, M. A. Endsley, M. A. McIntosh, A. C. Maue, W. R. Waters, D. R. Lee, and D. M. Estes Characterization of Bovine Homologues of Granulysin and NK-lysin J. Immunol., August 15, 2004; 173(4): 2607 - 2614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Neely, S. Epelman, L. L. Ma, P. Colarusso, C. J. Howlett, E. K. Amankwah, A. C. McIntyre, S. M. Robbins, and C. H. Mody Monocyte Surface-Bound IL-15 Can Function as an Activating Receptor and Participate in Reverse Signaling J. Immunol., April 1, 2004; 172(7): 4225 - 4234. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
