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Blood, 15 January 2009, Vol. 113, No. 3, pp. 612-621. Prepublished online as a Blood First Edition Paper on October 1, 2008; DOI 10.1182/blood-2008-06-159442. This Article Full Text (PDF) All Versions of this Article: blood-2008-06-159442v1 113/3/612    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Paiardini, M. Articles by Silvestri, G. Search for Related Content PubMed PubMed Citation Articles by Paiardini, M. Articles by Silvestri, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 2, 2008 Accepted September 2, 2008 Bone marrow-based homeostatic proliferation of mature T-cells in non-human primates: implications for AIDS pathogenesis Mirko Paiardini, Barbara Cervasi, Jessica C Engram, Shari N Gordon, Nichole R Klatt, Alagarraju Muthukumar, James Else, Robert S Mittler, Silvija I Staprans, Donald L Sodora, and Guido Silvestri* Department of Pathology, University of Pennsylvania, School of Medicine, Philadelphia, PA, United States Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States Department of Medicine, University of Texas Southwestern, Dallas, TX, United States Merck Vaccines, West Point, PA, United States Seattle Biomedical Research Institute, Seattle, WA, United States * Corresponding author; email: gsilvest{at}mail.med.upenn.edu. Bone marrow (BM) is the key hematopoietic organ in mammals and is involved in the homeostatic proliferation of memory CD8+ T-cells. Here, we expanded upon our previous observation that BM is a preferential site for T-cell proliferation in Simian Immunodeficiency Virus (SIV)-infected sooty mangabeys (SMs) that do not progress to AIDS despite high viremia. We found high levels of mature T-cell proliferation, involving both naive and memory cells, in healthy SMs and rhesus macaques (RMs). In addition, we observed in both species that lineage-specific, BM-based T-cell proliferation follows antibody-mediated in vivo CD4+ or CD8+ T-cell depletion, thus indicating a role for the BM in maintaining T-cell homeostasis under depleting circumstances. We also observed that, in SIV-infected SMs, but not RMs, the level of proliferation of BM-based CD4+ T-cells is higher than that of circulating CD4+ T-cells. Interestingly, limited BM-based CD4+ T-cell proliferation was found in SIV-infected SMs with low CD4+ T-cell counts, suggesting a regenerative failure in these animals. Collectively, these results indicate that BM is involved in maintaining T-cell homeostasis in primates, and suggest a role for BM-based CD4+ T-cell proliferation in determining the benign nature of natural SIV infection of SMs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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