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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2049-2057. Prepublished online as a Blood First Edition Paper on January 5, 2007; DOI 10.1182/blood-2006-03-009720. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-009720v1 blood-2006-03-009720v2 109/5/2049    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zheng, C. F. Articles by Mody, C. H. Search for Related Content PubMed PubMed Citation Articles by Zheng, C. F. Articles by Mody, C. H. Related Collections Immunobiology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and activation of this pathway is defective in HIV patients Chun Fu Zheng1, Ling Ling Ma2, Gareth J. Jones1, M. John Gill1, Alan M. Krensky4, Paul Kubes3, and Christopher H. Mody1,2 Departments of1 Microbiology and Infectious Disease, 2 Internal Medicine, and 3 Physiology and Biophysics, University of Calgary, AB, Canada; 4 Department of Pediatrics, Stanford University School of Medicine, CA An important mechanism of host defense to Cryptococcus neoformans involves the direct microbicidal activity of lymphocytes. The importance of CD4+ T cells is illustrated by the incidence of this infection in the acquired immunodeficiency syndrome (AIDS) patients; however, the relative activity of microbicidal CD4+ T cells compared with CD8+ T cells and natural killer (NK) cells has not been established. Further, although NK cells and CD8+ T cells use perforin or granulysin, respectively, to kill C neoformans, the effector molecule used by CD4+ T cells is not known. Experiments demonstrated that IL-2–activated peripheral blood lymphocytes from healthy adults acquire anticryptococcal activity, and surprisingly, that CD4+ T cells had the most profound effect on this activity. Using SrCl2induced degranulation and siRNA knockdown, granulysin was shown to be the effector molecule. Although activation by anti–CD3 + IL-2 resulted in the additional expression of perforin, this did not improve the anticryptococcal activity. Cryptococcal killing by CD4+ T cells was defective in human immunodeficiency virus (HIV)–infected patients due to dysregulated granulysin and perforin production in response to IL-2 or anti–CD3 + IL-2. In conclusion, CD4+ T cells are the major subset of cells responsible for killing C neoformans in peripheral blood. These cells use granulysin as the effector molecule, and priming is dysregulated in HIV-infected patients, which results in defective microbicidal activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. F. Zheng, G. J. Jones, M. Shi, J. C. D. Wiseman, K. J. Marr, B. M. Berenger, S. M. Huston, M. J. Gill, A. M. Krensky, P. Kubes, et al. Late Expression of Granulysin by Microbicidal CD4+ T Cells Requires PI3K- and STAT5-Dependent Expression of IL-2R{beta} That Is Defective in HIV-Infected Patients J. Immunol., June 1, 2008; 180(11): 7221 - 7229. [Abstract] [Full Text] [PDF]

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