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Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-03-0927. This Article Full Text (PDF) All Versions of this Article: 2003-03-0927v1 102/9/3244    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 Jankovic, V. Articles by Nikolich-Zugich, J. Search for Related Content PubMed PubMed Citation Articles by Jankovic, V. Articles by Nikolich-Zugich, J. Social Bookmarking                   What's this? Submitted March 26, 2003 Accepted June 8, 2003 Phenotypic and functional T-cell aging in Rhesus Macaques (Macaca mulatta): differential behavior of CD4 and CD8 subsets Vladimir Jankovic, Ilhem Messaoudi, and Janko Nikolich-Zugich* Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA; Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA * Corresponding author; email: nikolich{at}ohsu.edu. A prominent theory of immune senescence holds that repeated antigenic stimulation and decreased production of naive cells combine to progressively exhaust the reserve of lymphocytes available to fight new pathogens, culminating in an accumulation of lymphocytes that achieved replicative senescence. A well-defined primate model of immune senescence in vivo would greatly facilitate testing of this theory. Here, we investigated phenotypic and functional T-cell aging in the rhesus macaques (RM), currently the dominant primate model of AIDS. Our results show that sharp differences exist between the CD8 and CD4 T-cell subsets in: (i) cell cycle programs (as assessed by both in vitro proliferation and in vivo turnover measurement); (ii) CD28 regulation upon cell cycle entry; (iii) accumulation of immediate effector cells amongst the CD28- cells, believed to be close to or at replicative senescence. These results further suggest poor reliability of CD28 as a marker for senescence. We suggest that some of the T-cell aging phenomenology in RM can be ascribed to accentuation over time of the inherent differences in activation programs in CD8 and CD4 T-cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Stacy, A. Pasquali, V. L. Sexton, A. M. Cantwell, E. Kraig, and P. H. Dube An Age-Old Paradigm Challenged: Old Baboons Generate Vigorous Humoral Immune Responses to LcrV, A Plague Antigen J. Immunol., July 1, 2008; 181(1): 109 - 115. [Abstract] [Full Text] [PDF] L. Cicin-Sain, I. Messaoudi, B. Park, N. Currier, S. Planer, M. Fischer, S. Tackitt, D. Nikolich-Zugich, A. Legasse, M. K. Axthelm, et al. Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates PNAS, December 11, 2007; 104(50): 19960 - 19965. [Abstract] [Full Text] [PDF] I. Messaoudi, J. Warner, M. Fischer, B. Park, B. Hill, J. Mattison, M. A. Lane, G. S. Roth, D. K. Ingram, L. J. Picker, et al. From the Cover: Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates PNAS, December 19, 2006; 103(51): 19448 - 19453. [Abstract] [Full Text] [PDF] I. Messaoudi, J. Warner, D. Nikolich-Zugich, M. Fischer, and J. Nikolich-Zugich Molecular, Cellular, and Antigen Requirements for Development of Age-Associated T Cell Clonal Expansions In Vivo J. Immunol., January 1, 2006; 176(1): 301 - 308. [Abstract] [Full Text] [PDF] Y. Sun, J. E. Schmitz, P. M. Acierno, S. Santra, R. A. Subbramanian, D. H. Barouch, D. A. Gorgone, M. A. Lifton, K. R. Beaudry, K. Manson, et al. Dysfunction of Simian Immunodeficiency Virus/Simian Human Immunodeficiency Virus-Induced IL-2 Expression by Central Memory CD4+ T Lymphocytes J. Immunol., April 15, 2005; 174(8): 4753 - 4760. [Abstract] [Full Text] [PDF] I. Messaoudi, J. LeMaoult, J. A. Guevara-Patino, B. M. Metzner, and J. Nikolich-Zugich Age-related CD8 T Cell Clonal Expansions Constrict CD8 T Cell Repertoire and Have the Potential to Impair Immune Defense J. Exp. Med., November 15, 2004; 200(10): 1347 - 1358. [Abstract] [Full Text] [PDF] I. Kang, M. S. Hong, H. Nolasco, S. H. Park, J. M. Dan, J.-Y. Choi, and J. Craft Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine J. Immunol., July 1, 2004; 173(1): 673 - 681. [Abstract] [Full Text] [PDF]

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