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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.


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IMMUNOBIOLOGY

Bone marrow–based homeostatic proliferation of mature T cells in nonhuman primates: implications for AIDS pathogenesis

Mirko Paiardini1,*, Barbara Cervasi1,*, Jessica C. Engram1, Shari N. Gordon1, Nichole R. Klatt1,2, Alagarraju Muthukumar3, James Else2, Robert S. Mittler2, Silvija I. Staprans4, Donald L. Sodora5, and Guido Silvestri1,2

1 Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia; 2 Yerkes National Primate Research Center, Emory University, Atlanta, GA; 3 Department of Medicine, University of Texas Southwestern, Dallas; 4 Merck & Co Inc Vaccines, West Point, PA; and 5 Seattle Biomedical Research Institute, WA

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 on 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.


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