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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 17, 2006 Accepted December 14, 2006 Differential effects of IL-21 and IL-15 on perforin expression, lysosomal degranulation and proliferation in CD8 T cells of patients infected with Human Immunodeficiency Virus-1 (HIV) Lesley White, Subramaniam Krishnan, Natasa Strbo, Huanliang Liu, Michael A Kolber, Mathias G Lichtenheld, Rajendra Pahwa, and Savita Pahwa* Center for HIV Research, University of Miami Miller School of Medicine, Miami, FL Dept of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL Dept of Medicine, University of Miami Miller School of Medicine, Miami, FL Sylvester Comprehensive Cancer Center, Miami, FL Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL * Corresponding author; email: spahwa{at}med.miami.edu. An urgent need exists to devise strategies to augment antiviral immune responses in HIV-infected patients 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 CD4<50 copies/mL and CD4 counts >200 cells/mm3. Patient CD8 T cells displayed skewed maturation and decreased perforin expression as compared to healthy controls. Culture of freshly isolated patient PBMC for 5 hours to 5 days with IL-21 resulted in upregulation 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 TCR-induced degranulation. Treatment of patient PBMC 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 cells of healthy volunteers. We conclude that CD8 T cells of HIV infected patients 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 for anti-HIV immunotherapy. 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. Makedonas, P. P. Banerjee, R. Pandey, A. R. Hersperger, K. B. Sanborn, G. A. D. Hardy, J. S. Orange, and M. R. Betts Rapid Up-Regulation and Granule-Independent Transport of Perforin to the Immunological Synapse Define a Novel Mechanism of Antigen-Specific CD8+ T Cell Cytotoxic Activity J. Immunol., May 1, 2009; 182(9): 5560 - 5569. [Abstract] [Full Text] [PDF] A. L. Kinter, E. J. Godbout, J. P. McNally, I. Sereti, G. A. Roby, M. A. O'Shea, and A. S. Fauci The Common {gamma}-Chain Cytokines IL-2, IL-7, IL-15, and IL-21 Induce the Expression of Programmed Death-1 and Its Ligands J. Immunol., November 15, 2008; 181(10): 6738 - 6746. [Abstract] [Full Text] [PDF] Y. Enose-Akahata, U. Oh, C. Grant, and S. Jacobson Retrovirally induced CTL degranulation mediated by IL-15 expression and infection of mononuclear phagocytes in patients with HTLV-I-associated neurologic disease Blood, September 15, 2008; 112(6): 2400 - 2410. [Abstract] [Full Text] [PDF] M. J. Smyth, M. W.L. Teng, J. Sharkey, J. A. Westwood, N. M. Haynes, H. Yagita, K. Takeda, P. V. Sivakumar, and M. H. Kershaw Interleukin 21 Enhances Antibody-Mediated Tumor Rejection Cancer Res., April 15, 2008; 68(8): 3019 - 3025. [Abstract] [Full Text] [PDF] I. D. Davis, K. Skak, M. J. Smyth, P. E.G. Kristjansen, D. M. Miller, and P. V. Sivakumar Interleukin-21 Signaling: Functions in Cancer and Autoimmunity Clin. Cancer Res., December 1, 2007; 13(23): 6926 - 6932. [Abstract] [Full Text] [PDF]

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