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Journal of Virology, October 2002, p. 9981-9990, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9981-9990.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Decreased Levels of Recent Thymic Emigrants in Peripheral Blood of Simian Immunodeficiency Virus-Infected Macaques Correlate with Alterations within the Thymus

Donald L. Sodora,1* Jeffrey M. Milush,1 Felecia Ware,1 Aneta Wozniakowski,1 Lisa Montgomery,1 Harold M. McClure,2 Andrew A. Lackner,3 Marta Marthas,4 Vanessa Hirsch,5 R. Paul Johnson,6 Daniel C. Douek,7 and Richard A. Koup7

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas,1 Yerkes Regional Primate Research Center, Atlanta, Georgia,2 Tulane Regional Primate Research Center, Covington, Louisiana,3 California Regional Primate Research Center, Davis, California,4 New England Regional Primate Research Center, Southborough, Massachusetts,6 Vaccine Research Center,7 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland5

Received 4 April 2002/ Accepted 1 July 2002

The thymus is responsible for de novo production of CD4+ and CD8+ T cells and therefore is essential for T-cell renewal. The goal of this study was to assess the impact of simian immunodeficiency virus (SIV) infection on the production of T cells by the thymus. Levels of recent thymic emigrants within the peripheral blood were assessed through quantification of macaque T-cell receptor excision circles (TREC). Comparison of SIV-infected macaques (n = 15) to uninfected macaques (n = 23) revealed stable or increased TREC levels at 20 to 34 weeks postinfection. Further assessment of SIV-infected macaques (n = 4) determined that TREC levels decreased between 24 and 48 weeks postinfection. Through the assessment of longitudinal time points in three additional SIVmac239-infected macaques, the SIV infection was divided into two distinct phases. During phase 1 (16 to 30 weeks), TREC levels remained stable or increased within both the CD4 and CD8 T-cell populations. During phase 2 (after 16 to 30 weeks), TREC levels declined in both T-cell populations. As has been described for human immunodeficiency virus (HIV)-infected patients, this decline in TREC levels did at times correlate with an increased level of T-cell proliferation (Ki67+ cells). However, not all TREC decreases could be attributed to increased T-cell proliferation. Further evidence for thymic dysfunction was observed directly in a SIVmac239-infected macaque that succumbed to simian AIDS at 65 weeks postinfection. The thymus of this macaque contained an increased number of memory/effector CD8+ T cells and an increased level of apoptotic cells. In summary, reduced levels of TREC can be observed beginning at 16 to 30 weeks post-SIV infection and correlate with changes indicative of dysfunction within the thymic tissue. SIV infection of macaques will be a useful model system to elucidate the mechanisms responsible for the thymic dysfunction observed in HIV-infected patients.

* Corresponding author. Mailing address: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9113. Phone: (214) 648-2438. Fax: (214) 648-0231. E-mail: Donald.Sodora{at}UTSouthwestern.edu.

Journal of Virology, October 2002, p. 9981-9990, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9981-9990.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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