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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 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 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 Google Scholar Articles by Brockman, M. A. Articles by Kaufmann, D. E. PubMed PubMed Citation Articles by Brockman, M. A. Articles by Kaufmann, D. E. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells Mark A. Brockman1,2,*, Douglas S. Kwon13,*, Daniel P. Tighe1, David F. Pavlik1, Pamela C. Rosato1, Jennifer Sela1, Filippos Porichis1,2, Sylvie Le Gall1,2, Michael T. Waring1,3, Kristin Moss1, Heiko Jessen4, Florencia Pereyra1,2,5, Daniel G. Kavanagh1,2, Bruce D. Walker13, and Daniel E. Kaufmann1,2 1 Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Massachusetts General Hospital, Charlestown; 2 Harvard Medical School, Boston, MA; 3 Howard Hughes Medical Institute, Chevy Chase, MD; 4 Jessen Praxis, Berlin, Germany; and 5 Brigham and Women's Hospital, Boston, MA Murine models indicate that interleukin-10 (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 up-regulated 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 peripheral blood mononuclear cells (PBMCs), correlated positively with viral load and diminished after successful antiretroviral therapy. IL-10 mRNA levels were up-regulated in multiple PBMC subsets in HIV-infected subjects compared with HIV-negative controls, particularly in T, B, and natural killer (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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