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Dynamics of T- and B-Lymphocyte Turnover in a Natural Host of Simian Immunodeficiency Virus

Amitinder Kaur,^1* Michele Di Mascio,² Amy Barabasz,¹ Michael Rosenzweig,^1, Harold M. McClure,^3, Alan S. Perelson,⁴ Ruy M. Ribeiro,⁴ and R. Paul Johnson^1,5

Division of Immunology, Harvard Medical School, New England Primate Research Center, One Pine Hill Drive, Southborough, Massachusetts 01772-9102,¹ Biostatistics Research Branch, Office of Clinical Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892,² Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322,³ Los Alamos National Laboratory, Los Alamos, New Mexico 87545,⁴ Infectious Disease Unit and Partners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts 02115⁵

Received 6 October 2007/ Accepted 12 November 2007

Increased lymphocyte turnover is a hallmark of pathogenic lentiviral infection. To investigate perturbations in lymphocyte dynamics in natural hosts with nonpathogenic simian immunodeficiency virus (SIV) infection, the nucleoside analog bromodeoxyuridine (BrdU) was administered to six naturally SIV-infected and five SIV-negative sooty mangabeys. As a measure of lymphocyte turnover, we estimated the mean death rate by fitting a mathematical model to the fraction of BrdU-labeled cells during a 2-week labeling and a median 10-week delabeling period. Despite significantly lower total T- and B-lymphocyte counts in SIV-infected sooty mangabeys than in SIV-negative mangabeys, the turnover rate of B lymphocytes and CD4⁺ and CD8⁺ T lymphocytes was not increased in the SIV-infected animals. A small, rapidly proliferating CD45RA⁺ memory subset and a large, slower-proliferating CD45RA^– central memory subset of CD4⁺ T lymphocytes identified in the peripheral blood of sooty mangabeys also did not show evidence of increased turnover in the context of SIV infection. Independently of SIV infection, the turnover of CD4⁺ T lymphocytes in sooty mangabeys was significantly higher (P < 0.01) than that of CD8⁺ T lymphocytes, a finding hitherto not reported in rhesus macaques or humans. The absence of aberrant T-lymphocyte turnover along with an inherently high rate of CD4⁺ T-lymphocyte turnover may help to preserve the pool of central memory CD4⁺ T lymphocytes in viremic SIV-infected sooty mangabeys and protect against progression to AIDS.

Published ahead of print on 21 November 2007.

Present address: Tolerx, Inc., 300 Technology Square, Cambridge, MA 02139.

Deceased.