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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3873-3880. Prepublished online as a Blood First Edition Paper on December 27, 2006; DOI 10.1182/blood-2006-09-045278. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-09-045278v1 109/9/3873    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 White, L. Articles by Pahwa, S. Search for Related Content PubMed PubMed Citation Articles by White, L. Articles by Pahwa, S. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Differential effects of IL-21 and IL-15 on perforin expression, lysosomal degranulation, and proliferation in CD8 T cells of patients with human immunodeficiency virus-1 (HIV) Lesley White1,2, Subramaniam Krishnan1,2, Natasa Strbo1,2, Huanliang Liu1,2, Michael A. Kolber1,3, Mathias G. Lichtenheld1,2,4, Rajendra N. Pahwa5, and Savita Pahwa1,2 1 Center for HIV Research, University of Miami Miller School of Medicine, Miami, FL; 2 Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL; 3 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL; 4 Sylvester Comprehensive Cancer Center, Miami, FL; 5 Diabetes Research Institute, University of Miami, Miller School of Medicine, Miami, FL An urgent need exists to devise strategies to augment antiviral immune responses in patients with HIV who are virologically well controlled and immunologically stable on highly active antiretroviral therapy (HAART). The objective of this study was to compare the immunomodulatory effects of the cytokines interleukin (IL)–21 with IL-15 on CD8 T cells in patients with HIV RNA of less than 50 copies/mL and CD4 counts greater than 200 cells/mm.3 Patient CD8 T cells displayed skewed maturation and decreased perforin expression compared with healthy controls. Culture of freshly isolated patient peripheral-blood mononuclear cells (PBMCs) for 5 hours to 5 days with IL-21 resulted in up-regulation of perforin in CD8 T cells, including memory and effector subsets and virus-specific T cells. IL-21 did not induce T-cell activation or proliferation, nor did it augment T-cell receptor (TCR)–induced degranulation. Treatment of patient PBMCs with IL-15 resulted in induction of perforin in association with lymphocyte proliferation and augmentation of TCR-induced degranulation. Patient CD8 T cells were more responsive to cytokine effects than the cells of healthy volunteers. We conclude that CD8 T cells of patients with HIV can be modulated by IL-21 to increase perforin expression without undergoing overt cellular activation. IL-21 could potentially be useful for its perforin-enhancing properties in anti-HIV immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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