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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2382-2390. Prepublished online as a Blood First Edition Paper on June 16, 2005; DOI 10.1182/blood-2005-04-1403. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1403v1 106/7/2382    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 Potula, R. Articles by Persidsky, Y. Search for Related Content PubMed PubMed Citation Articles by Potula, R. Articles by Persidsky, Y. Related Collections Immunobiology Phagocytes Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Inhibition of indoleamine 2,3-dioxygenase (IDO) enhances elimination of virus-infected macrophages in an animal model of HIV-1 encephalitis Raghava Potula, Larisa Poluektova, Bryan Knipe, Jesse Chrastil, David Heilman, Huanyu Dou, Osamu Takikawa, David H. Munn, Howard E. Gendelman, and Yuri Persidsky From the Center for Neurovirology and Neurodegenerative Disorders, Departments of Pharmacology and Experimental Neurosciences, Pathology/Microbiology and Internal Medicine, University of Nebraska Medical Center, Omaha, NE; Central Research Institute, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; and the Institute for Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA. Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism. IDO activity is linked with immunosuppression by its ability to inhibit lymphocyte proliferation, and with neurotoxicity through the generation of quinolinic acid and other toxins. IDO is induced in macrophages by HIV-1 infection, and it is up regulated in macrophages in human brain tissue with HIV-1 encephalitis (HIVE). Using a model of HIVE, we investigated whether IDO inhibitor 1-methyl-D-tryptophan (1-MT) could affect the generation of cytotoxic T lymphocytes (CTLs) and clearance of virus-infected macrophages from the brain. Severe combined immunodeficient mice were reconstituted with human peripheral blood lymphocytes, and encephalitis was induced by intracranial injection of autologous HIV-1-infected monocyte-derived macrophages (MDMs). Animals treated with 1-MT demonstrated increased numbers of human CD3+, CD8+, CD8+/interferon-+ T cells, and HIV-1gag/pol-specific CTLs in peripheral blood compared with controls. At week 2 after MDM injection in the basal ganglia, mice treated with 1-MT showed a 2-fold increase in CD8+ T lymphocytes in the areas of the brain containing HIV-1-infected MDMs compared with untreated controls. By week 3, 1-MT-treated mice showed 89% reduction in HIV-infected MDMs in brain as compared with controls. Thus, manipulation of immunosuppressive IDO activity in HIVE may enhance the generation of HIV-1-specific CTLs, leading to elimination of HIV-1-infected macrophages in brain. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: IDO production, adaptive immunity, and CTL killing Thomas Luft, Eugene Maraskovsky, and Max Schnurr Blood 2005 106: 2228-2229. [Full Text] [PDF] This article has been cited by other articles: A. Boasso, M. 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