| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Vaccine Research Center and
Laboratory of Immunoregulation, Clinical and Molecular Retrovirology Section, National Institute of Allergy and Infectious Diseases,
Department of Experimental Transplantation and Immunology, Medicine Branch, National Cancer Institute, and
Critical Care Medicine Department, Warren Magnusen Clinical Center, National Institutes of Health, Bethesda, MD 20892;
¶ Department of Medicine, University of California, San Diego, CA 92103;
||
Science Applications International Corporation-Frederick, Clinical Services Program, Frederick Cancer Research and Development Center, Frederick, MD 21702;
#
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; and
**
San Diego Veterans Affairs Medical Center, La Jolla, CA 92093
The effects of HIV infection upon the thymus and peripheral T cell turnover have been implicated in the pathogenesis of AIDS. In this study, we investigated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR rearrangement excision circles (TREC) and parameters of cell proliferation, including Ki67 expression and ex vivo bromodeoxyuridine incorporation in 22 individuals with early untreated HIV disease and in 15 HIV-infected individuals undergoing temporary interruption of therapy. We found an inverse association between increased T cell proliferation with rapid viral recrudescence and a decrease in TREC levels. However, during early HIV infection, we found that CD45RO-CD27high (naive) CD4+ T cell proliferation did not increase, despite a loss of TREC within naive CD4+ T cells. A possible explanation for this is that decreased thymic output occurs in HIV-infected humans. This suggests that the loss of TREC during HIV infection can arise from a combination of increased T cell proliferation and decreased thymic output, and that both mechanisms can contribute to the perturbations in T cell homeostasis that underlie the pathogenesis of AIDS.
This article has been cited by other articles:
|
|
 |
|
  M. E. Bull, G. H. Learn, S. McElhone, J. Hitti, D. Lockhart, S. Holte, J. Dragavon, R. W. Coombs, J. I. Mullins, and L. M. Frenkel Monotypic Human Immunodeficiency Virus Type 1 Genotypes across the Uterine Cervix and in Blood Suggest Proliferation of Cells with Provirus J. Virol., June 15, 2009; 83(12): 6020 - 6028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. M. Borghans and K. Tesselaar Be fruitful, multiply, and replenish Blood, May 28, 2009; 113(22): 5369 - 5370. [Full Text] [PDF]
|
|
|
|
|
|
I. Bains, R. Antia, R. Callard, and A. J. Yates Quantifying the development of the peripheral naive CD4+ T-cell pool in humans Blood, May 28, 2009; 113(22): 5480 - 5487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Vrisekoop, I. den Braber, A. B. de Boer, A. F. C. Ruiter, M. T. Ackermans, S. N. van der Crabben, E. H. R. Schrijver, G. Spierenburg, H. P. Sauerwein, M. D. Hazenberg, et al. Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool PNAS, April 22, 2008; 105(16): 6115 - 6120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vranjkovic, A. M. Crawley, K. Gee, A. Kumar, and J. B. Angel IL-7 decreases IL-7 receptor {alpha} (CD127) expression and induces the shedding of CD127 by human CD8+ T cells Int. Immunol., December 1, 2007; 19(12): 1329 - 1339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Nie, G. D. Bren, S. R. Vlahakis, A. A. Schimnich, J. M. Brenchley, S. A. Trushin, S. Warren, D. J. Schnepple, C. M. Kovacs, M. R. Loutfy, et al. Human Immunodeficiency Virus Type 1 Protease Cleaves Procaspase 8 In Vivo J. Virol., July 1, 2007; 81(13): 6947 - 6956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Biancotto, J.-C. Grivel, S. J. Iglehart, C. Vanpouille, A. Lisco, S. F. Sieg, R. Debernardo, K. Garate, B. Rodriguez, L. B. Margolis, et al. Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1 Blood, May 15, 2007; 109(10): 4272 - 4279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Dion, R. Bordi, J. Zeidan, R. Asaad, M.-R. Boulassel, J.-P. Routy, M. M. Lederman, R.-P. Sekaly, and R. Cheynier Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection Blood, April 1, 2007; 109(7): 2912 - 2920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Shen, H.-C. Yang, Y. Zhou, A. J. Chase, J. D. Boyer, H. Zhang, J. B. Margolick, M. C. Zink, J. E. Clements, and R. F. Siliciano Novel Pathway for Induction of Latent Virus from Resting CD4+ T Cells in the Simian Immunodeficiency Virus/Macaque Model of Human Immunodeficiency Virus Type 1 Latency J. Virol., February 15, 2007; 81(4): 1660 - 1670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. VandeWoude and C. Apetrei Going Wild: Lessons from Naturally Occurring T-Lymphotropic Lentiviruses Clin. Microbiol. Rev., October 1, 2006; 19(4): 728 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Delobel, M.-T. Nugeyre, M. Cazabat, K. Sandres-Saune, C. Pasquier, L. Cuzin, B. Marchou, P. Massip, R. Cheynier, F. Barre-Sinoussi, et al. Naive T-cell depletion related to infection by x4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy. J. Virol., October 1, 2006; 80(20): 10229 - 10236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. van den Dool and R. J. de Boer The Effects of Age, Thymectomy, and HIV Infection on {alpha} and beta TCR Excision Circles in Naive T Cells J. Immunol., October 1, 2006; 177(7): 4391 - 4401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. Schacker, J. M. Brenchley, G. J. Beilman, C. Reilly, S. E. Pambuccian, J. Taylor, D. Skarda, M. Larson, D. C. Douek, and A. T. Haase Lymphatic Tissue Fibrosis Is Associated with Reduced Numbers of Naive CD4+ T Cells in Human Immunodeficiency Virus Type 1 Infection. Clin. Vaccine Immunol., May 1, 2006; 13(5): 556 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Migliaccio, P. M. S. Alves, P. Romero, and N. Rufer Distinct Mechanisms Control Human Naive and Antigen-Experienced CD8+ T Lymphocyte Proliferation J. Immunol., February 15, 2006; 176(4): 2173 - 2182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Chu, S. A. Memon, S. O. Sharrow, F. T. Hakim, M. Eckhaus, P. J. Lucas, and R. E. Gress Exogenous IL-7 increases recent thymic emigrants in peripheral lymphoid tissue without enhanced thymic function Blood, August 15, 2004; 104(4): 1110 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nobile, R. Correa, J. A. M. Borghans, C. D'Agostino, P. Schneider, R. J. de Boer, and G. Pantaleo De novo T-cell generation in patients at different ages and stages of HIV-1 disease Blood, July 15, 2004; 104(2): 470 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Krenger, H. Schmidlin, G. Cavadini, and G. A. Hollander On the Relevance of TCR Rearrangement Circles as Molecular Markers for Thymic Output during Experimental Graft-versus-Host Disease J. Immunol., June 15, 2004; 172(12): 7359 - 7367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Feeney, R. Draenert, K. A. Roosevelt, S. I. Pelton, K. McIntosh, S. K. Burchett, C. Mao, B. D. Walker, and P. J. R. Goulder Reconstitution of Virus-Specific CD4 Proliferative Responses in Pediatric HIV-1 Infection J. Immunol., December 15, 2003; 171(12): 6968 - 6975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Efroni, D. Harel, and I. R. Cohen Toward Rigorous Comprehension of Biological Complexity: Modeling, Execution, and Visualization of Thymic T-Cell Maturation Genome Res., November 1, 2003; 13(11): 2485 - 2497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Stove, E. Naessens, C. Stove, T. Swigut, J. Plum, and B. Verhasselt Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development Blood, October 15, 2003; 102(8): 2925 - 2932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Monceaux, R. H. T. Fang, M. C. Cumont, B. Hurtrel, and J. Estaquier Distinct Cycling CD4+- and CD8+-T-Cell Profiles during the Asymptomatic Phase of Simian Immunodeficiency Virus SIVmac251 Infection in Rhesus Macaques J. Virol., September 15, 2003; 77(18): 10047 - 10059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. O. Schonland, J. K. Zimmer, C. M. Lopez-Benitez, T. Widmann, K. D. Ramin, J. J. Goronzy, and C. M. Weyand Homeostatic control of T-cell generation in neonates Blood, August 15, 2003; 102(4): 1428 - 1434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Shen, M. C. Zink, J. L. Mankowski, K. Chadwick, J. B. Margolick, L. M. Carruth, M. Li, J. E. Clements, and R. F. Siliciano Resting CD4+ T Lymphocytes but Not Thymocytes Provide a Latent Viral Reservoir in a Simian Immunodeficiency Virus-Macaca nemestrina Model of Human Immunodeficiency Virus Type 1-Infected Patients on Highly Active Antiretroviral Therapy J. Virol., April 15, 2003; 77(8): 4938 - 4949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Pham, M. Belzer, J. A. Church, C. Kitchen, C. M. Wilson, S. D. Douglas, Y. Geng, M. Silva, R. M. Mitchell, and P. Krogstad Assessment of Thymic Activity in Human Immunodeficiency Virus-Negative and -Positive Adolescents by Real-Time PCR Quantitation of T-Cell Receptor Rearrangement Excision Circles Clin. Vaccine Immunol., March 1, 2003; 10(2): 323 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Ribeiro, H. Mohri, D. D. Ho, and A. S. Perelson In vivo dynamics of T cell activation, proliferation, and death in HIV-1 infection: Why are CD4+ but not CD8+ T cells depleted? PNAS, November 26, 2002; 99(24): 15572 - 15577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Lewin, R. M. Ribeiro, G. R. Kaufmann, D. Smith, J. Zaunders, M. Law, A. Solomon, P. U. Cameron, D. Cooper, and A. S. Perelson Dynamics of T Cells and TCR Excision Circles Differ After Treatment of Acute and Chronic HIV Infection J. Immunol., October 15, 2002; 169(8): 4657 - 4666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Sodora, J. M. Milush, F. Ware, A. Wozniakowski, L. Montgomery, H. M. McClure, A. A. Lackner, M. Marthas, V. Hirsch, R. P. Johnson, et al. Decreased Levels of Recent Thymic Emigrants in Peripheral Blood of Simian Immunodeficiency Virus-Infected Macaques Correlate with Alterations within the Thymus J. Virol., August 28, 2002; 76(19): 9981 - 9990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Terra, N. Labrecque, and C. Perreault Thymic and Extrathymic T Cell Development Pathways Follow Different Rules J. Immunol., July 15, 2002; 169(2): 684 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ye and D. E. Kirschner Reevaluation of T Cell Receptor Excision Circles as a Measure of Human Recent Thymic Emigrants J. Immunol., May 15, 2002; 168(10): 4968 - 4979. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
