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Blood, 9 July 2009, Vol. 114, No. 2, pp. 346-356. Prepublished online as a Blood First Edition Paper on April 13, 2009; DOI 10.1182/blood-2008-12-191296. This Article Full Text (PDF) Supplemental Methods, Table, and Figures All Versions of this Article: blood-2008-12-191296v1 114/2/346    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 Brockman, M. A. Articles by Kaufmann, D. E. Search for Related Content PubMed PubMed Citation Articles by Brockman, M. A. Articles by Kaufmann, D. E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 3, 2008 Accepted March 25, 2009 IL-10 is upregulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells Mark A. Brockman, Douglas S. Kwon, Daniel P. Tighe, David F. Pavlik, Pamela C. Rosato, Jennifer Sela, Filippos Porichis, Sylvie Le Gall, Michael T. Waring, Kristin Moss, Heiko Jessen, Florencia Pereyra, Daniel G. Kavanagh, Bruce D. Walker, and Daniel E. Kaufmann* Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Charlestown, MA, United States Harvard Medical School, Boston, MA, United States Howard Hughes Medical Institute, Chevy Chase, MD, United States Jessen Praxis, Berlin, Germany Brigham and Women's Hospital, Boston, MA, United States * Corresponding author; email: dkaufmann{at}partners.org. Murine models indicate that IL-10 can suppress viral clearance, and interventional blockade of IL-10 activity has been proposed to enhance immunity in chronic viral infections. Increased IL-10 levels have been observed during HIV infection and IL-10 blockade has been shown to enhance T cell function in some HIV-infected subjects. However, the categories of individuals in whom the IL-10 pathway is upregulated are poorly defined, and the cellular sources of IL-10 in these subjects remain to be determined. Here we report that blockade of the IL-10 pathway augmented in vitro proliferative capacity of HIV-specific CD4 and CD8 T cells in individuals with ongoing viral replication. IL-10 blockade also increased cytokine secretion by HIV-specific CD4 T cells. Spontaneous IL-10 expression, measured as either plasma IL-10 protein or IL-10 mRNA in PBMC, correlated positively with viral load and diminished following successful antiretroviral therapy. IL-10 mRNA levels were upregulated in multiple PBMC subsets in HIV infected subjects compared to HIV-negative controls, particularly in T, B, and NK cells, whereas monocytes were a major source of IL-10 mRNA in HIV-infected and uninfected individuals. These data indicate that multiple cell types contribute to IL-10-mediated immune suppression in the presence of uncontrolled HIV viremia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Suppressing the suppressor David G. Brooks Blood 2009 114: 233. [Full Text] [PDF] This article has been cited by other articles: B. Slobedman, P. A. Barry, J. V. Spencer, S. Avdic, and A. Abendroth Virus-Encoded Homologs of Cellular Interleukin-10 and Their Control of Host Immune Function J. Virol., October 1, 2009; 83(19): 9618 - 9629. [Full Text] [PDF] S.-H. Lee, K.-S. Kim, N. Fodil-Cornu, S. M. Vidal, and C. A. Biron Activating receptors promote NK cell expansion for maintenance, IL-10 production, and CD8 T cell regulation during viral infection J. Exp. Med., September 28, 2009; 206(10): 2235 - 2251. [Abstract] [Full Text] [PDF] D. G. Brooks Suppressing the suppressor Blood, July 9, 2009; 114(2): 233 - 233. [Full Text] [PDF]

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