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The Journal of Immunology, 2005, 174: 4753-4760.
Copyright © 2005 by The American Association of Immunologists

Dysfunction of Simian Immunodeficiency Virus/Simian Human Immunodeficiency Virus-Induced IL-2 Expression by Central Memory CD4+ T Lymphocytes1

Yue Sun*, Jörn E. Schmitz*, Paula M. Acierno*, Sampa Santra*, Ramu A. Subbramanian*, Dan H. Barouch*, Darci A. Gorgone*, Michelle A. Lifton*, Kristin R. Beaudry*, Kelledy Manson{dagger}, Valerie Philippon{dagger}, Ling Xu{ddagger}, Holden T. Maecker§, John R. Mascola{ddagger}, Dennis Panicali{dagger}, Gary J. Nabel{ddagger} and Norman L. Letvin2,*,{ddagger}

* Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; {dagger} Therion Biologics, Cambridge, MA 02142; {ddagger} Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and § BD Biosciences, San Jose, CA 95131

Production of IL-2 and IFN-{gamma} by CD4+ T lymphocytes is important for the maintenance of a functional immune system in infected individuals. In the present study, we assessed the cytokine production profiles of functionally distinct subsets of CD4+ T lymphocytes in rhesus monkeys infected with pathogenic or attenuated SIV/simian human immunodeficiency virus (SHIV) isolates, and these responses were compared with those in vaccinated monkeys that were protected from immunodeficiency following pathogenic SHIV challenge. We observed that preserved central memory CD4+ T lymphocyte production of SIV/SHIV-induced IL-2 was associated with disease protection following primate lentivirus infection. Persisting clinical protection in vaccinated and challenged monkeys is thus correlated with a preserved capacity of the peripheral blood central memory CD4+ T cells to express this important immunomodulatory cytokine.




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