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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, 2007October 12, 2006; DOI 10.1182/blood-2006-03-009720. This Article 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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 14, 2006 Accepted October 5, 2006 Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans and activation of this pathway is defective in HIV patients Chun Fu Zheng, Lingling Ma, Gareth J Jones, M John Gill, Alan M. Krensky, Paul Kubes, and Christopher H Mody* University of Calgary, Canada Stanford University Medical Center * Corresponding author; email: cmody{at}ucalgary.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 AIDS patients; however, the relative activity of microbicidal CD4+ T cells compared to CD8+ T cells and NK cells has not been established. Further, although NK cells and CD8+ T cells utilize 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 anti-cryptococcal activity, and surprisingly, that CD4+ T cells had the most profound effect on this activity. Using SrCl2-induced 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 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: A. E. Hogg, G. C. Bowick, N. K. Herzog, M. W. Cloyd, and J. J. Endsley Induction of granulysin in CD8+ T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1 J. Leukoc. Biol., November 1, 2009; 86(5): 1191 - 1203. [Abstract] [Full Text] [PDF] G. J. Jones, J. C. D. Wiseman, K. J. Marr, S. Wei, J. Y. Djeu, and C. H. Mody In contrast to anti-tumor activity, YT cell and primary NK cell cytotoxicity for Cryptococcus neoformans bypasses LFA-1 Int. Immunol., April 1, 2009; 21(4): 423 - 432. [Abstract] [Full Text] [PDF] 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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