Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 29 November 1996:
Vol. 274. no. 5292, pp. 1543 - 1547
DOI: 10.1126/science.274.5292.1543

Reports

T Cell Telomere Length in HIV-1 Infection: No Evidence for Increased CD4+ T Cell Turnover

Katja C. Wolthers, G. Bea, A. Wisman, Sigrid A. Otto, Ana-Maria de Roda Husman, Niels Schaft, Frank de Wolf, Jaap Goudsmit, Roel A. Coutinho, Ate G. J. van der Zee, Linde Meyaard, Frank Miedema *

Progression to acquired immunodeficiency syndrome (AIDS) has been related to exhaustion of the regenerative capacity of the immune system resulting from high T cell turnover. Analysis of telomeric terminal restriction fragment (TRF) length, a marker for cellular replicative history, showed that CD8+ T cell TRF length decreased but CD4+ T cell TRF length was stable during the course of human immunodeficiency virus type-1 (HIV-1) infection, which was not explained by differential telomerase activity. This observation provides evidence that turnover in the course of HIV-1 infection can be increased considerably in CD8+ T cells, but not in CD4+ T cells. These results are compatible with CD4+ T cell decline in HIV-1 infection caused by interference with cell renewal.

K. C. Wolthers, S. A. Otto, A.-M. de Roda Husman, N. Schaft, L. Meyaard, Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology of the University of Amsterdam, Amsterdam, Netherlands.
G. B. A. Wisman and A. G. J. van der Zee, Department of Gynaecology and Obstetrics, Academic Hospital Groningen, University of Groningen, Groningen, Netherlands.
F. de Wolf and J. Goudsmit, Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
R. A. Coutinho, Department of Public Health, Municipal Health Service, Amsterdam, Netherlands.
F. Miedema, Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology of the University of Amsterdam, Amsterdam, Netherlands, and Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
*   To whom correspondence should be addressed at Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Department of Clinical Viro-Immunology, Plesmanlaan 125, 1066 CX Amsterdam, Netherlands. E-mail: clbkvi{at}xs4all.nl


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Telomerase activity of HIV-1-specific CD8+ T cells: constitutive up-regulation in controllers and selective increase by blockade of PD ligand 1 in progressors.
M. Lichterfeld, D. Mou, T. D. H. Cung, K. L. Williams, M. T. Waring, J. Huang, F. Pereyra, A. Trocha, G. J. Freeman, E. S. Rosenberg, et al. (2008)
Blood 112, 3679-3687
   Abstract »    Full Text »    PDF »
S-phase entry leads to cell death in circulating T cells from HIV-infected persons.
S. F. Sieg, D. A. Bazdar, and M. M. Lederman (2008)
J. Leukoc. Biol. 83, 1382-1387
   Abstract »    Full Text »    PDF »
HIV-Induced Changes in T Cell Signaling Pathways.
M. Schweneker, D. Favre, J. N. Martin, S. G. Deeks, and J. M. McCune (2008)
J. Immunol. 180, 6490-6500
   Abstract »    Full Text »    PDF »
Telomere dynamics in Fancg-deficient mouse and human cells.
S. Franco, H. J. van de Vrugt, P. Fernandez, M. Aracil, F. Arwert, and M. A. Blasco (2004)
Blood 104, 3927-3935
   Abstract »    Full Text »    PDF »
Distinct Cycling CD4+- and CD8+-T-Cell Profiles during the Asymptomatic Phase of Simian Immunodeficiency Virus SIVmac251 Infection in Rhesus Macaques.
V. Monceaux, R. H. T. Fang, M. C. Cumont, B. Hurtrel, and J. Estaquier (2003)
J. Virol. 77, 10047-10059
   Abstract »    Full Text »    PDF »
Differential Impairment of Lytic and Cytokine Functions in Senescent Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes.
M. Dagarag, H. Ng, R. Lubong, R. B. Effros, and O. O. Yang (2003)
J. Virol. 77, 3077-3083
   Abstract »    Full Text »    PDF »
Turnover Rates of B Cells, T Cells, and NK Cells in Simian Immunodeficiency Virus-Infected and Uninfected Rhesus Macaques.
R. J. De Boer, H. Mohri, D. D. Ho, and A. S. Perelson (2003)
J. Immunol. 170, 2479-2487
   Abstract »    Full Text »    PDF »
In vivo dynamics of T cell activation, proliferation, and death in HIV-1 infection: Why are CD4+ but not CD8+ T cells depleted?.
R. M. Ribeiro, H. Mohri, D. D. Ho, and A. S. Perelson (2002)
PNAS 99, 15572-15577
   Abstract »    Full Text »    PDF »
Increased peripheral expansion of naive CD4+ T cells in vivo after IL-2 treatment of patients with HIV infection.
V. Natarajan, R. A. Lempicki, I. Sereti, Y. Badralmaa, J. W. Adelsberger, J. A. Metcalf, D. A. Prieto, R. Stevens, M. W. Baseler, J. A. Kovacs, et al. (2002)
PNAS 99, 10712-10717
   Abstract »    Full Text »    PDF »
CD4 lymphocytes in the blood of HIV+ individuals migrate rapidly to lymph nodes and bone marrow: support for homing theory of CD4 cell depletion.
J. J-Y. Chen, J. C. Huang, M. Shirtliff, E. Briscoe, S. Ali, F. Cesani, D. Paar, and M. W. Cloyd (2002)
J. Leukoc. Biol. 72, 271-278
   Abstract »    Full Text »    PDF »
Telomeres, X-Inactivation Ratios, and Hematopoietic Stem Cell Transplantation in Humans: A Review.
I. Thornley and M. H. Freedman (2002)
Stem Cells 20, 198-204
   Abstract »    Full Text »    PDF »
Early hematopoietic reconstitution after clinical stem cell transplantation: evidence for stochastic stem cell behavior and limited acceleration in telomere loss.
I. Thornley, R. Sutherland, R. Wynn, R. Nayar, L. Sung, G. Corpus, T. Kiss, J. Lipton, J. Doyle, F. Saunders, et al. (2002)
Blood 99, 2387-2396
   Abstract »    Full Text »    PDF »
Identification of Dynamically Distinct Subpopulations of T Lymphocytes That Are Differentially Affected by HIV.
J. A. Kovacs, R. A. Lempicki, I. A. Sidorov, J. W. Adelsberger, B. Herpin, J. A. Metcalf, I. Sereti, M. A. Polis, R. T. Davey, J. Tavel, et al. (2001)
J. Exp. Med. 194, 1731-1741
   Abstract »    Full Text »    PDF »
Increased Turnover of T Lymphocytes in HIV-1 Infection and Its Reduction by Antiretroviral Therapy.
H. Mohri, A. S. Perelson, K. Tung, R. M. Ribeiro, B. Ramratnam, M. Markowitz, R. Kost, Hurley, L. Weinberger, D. Cesar, et al. (2001)
J. Exp. Med. 194, 1277-1288
   Abstract »    Full Text »    PDF »
The pathogenesis of HIV-1 infection.
J. Weber (2001)
Br. Med. Bull. 58, 61-72
   Abstract »    Full Text »    PDF »
Apoptosis in T-Lymphocyte Subsets in Human Immunodeficiency Virus-Infected Children Measured Immediately Ex Vivo and following In Vitro Activation.
T. Niehues, T. W. McCloskey, J. Ndagijimana, G. Horneff, V. Wahn, and S. Pahwa (2001)
Clin. Vaccine Immunol. 8, 74-78
   Abstract »    Full Text »    PDF »
Differential Dynamics of CD4+ and CD8+ T-Lymphocyte Proliferation and Activation in Acute Simian Immunodeficiency Virus Infection.
A. Kaur, C. L. Hale, S. Ramanujan, R. K. Jain, and R. P. Johnson (2000)
J. Virol. 74, 8413-8424
   Abstract »    Full Text »
Human Immunodeficiency Virus Type 1 Induces Apoptosis in CD4+ but Not in CD8+ T Cells in Ex Vivo-Infected Human Lymphoid Tissue.
J.-C. Grivel, N. Malkevitch, and L. Margolis (2000)
J. Virol. 74, 8077-8084
   Abstract »    Full Text »
Ineffective Cellular Immune Response Associated with T-Cell Apoptosis in Susceptible Mycobacterium bovis BCG-Infected Mice.
L. Kremer, J. Estaquier, I. Wolowczuk, F. Biet, J.-C. Ameisen, and C. Locht (2000)
Infect. Immun. 68, 4264-4273
   Abstract »    Full Text »    PDF »
CD4 T lymphocytes are primed to express Fas ligand by CD4 cross-linking and to contribute to CD8 T-cell apoptosis via Fas/FasL death signaling pathway.
M. Tateyama, N. Oyaizu, T. W. McCloskey, S. Than, and S. Pahwa (2000)
Blood 96, 195-202
   Abstract »    Full Text »    PDF »
Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy.
S. Fleury, G. P. Rizzardi, A. Chapuis, G. Tambussi, C. Knabenhans, E. Simeoni, J.-Y. Meuwly, J.-M. Corpataux, A. Lazzarin, F. Miedema, et al. (2000)
PNAS 97, 5393-5398
   Abstract »    Full Text »    PDF »
In vivo HIV-1 infection of CD45RA+CD4+ T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4+ T cell decline.
H. Blaak, A. B. van't Wout, M. Brouwer, B. Hooibrink, E. Hovenkamp, and H. Schuitemaker (2000)
PNAS 97, 1269-1274
   Abstract »    Full Text »    PDF »
T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART).
M. D. Hazenberg, J. W. T. C. Stuart, S. A. Otto, J. C. C. Borleffs, C. A. B. Boucher, R. J. de Boer, F. Miedema, and D. Hamann (2000)
Blood 95, 249-255
   Abstract »    Full Text »    PDF »
The potential importance of HIV-induction of lymphocyte homing to lymph nodes.
J. J.-Y. Chen and M. W. Cloyd (1999)
Int. Immunol. 11, 1591-1594
   Abstract »    Full Text »    PDF »
Distribution of Cycling T Lymphocytes in Blood and Lymphoid Organs During Immune Responses.
F. Vasseur, A. Le Campion, J. H. Pavlovitch, and C. Penit (1999)
J. Immunol. 162, 5164-5172
   Abstract »    Full Text »    PDF »
Rapid Telomere Shortening in Children.
S. L. Zeichner, P. Palumbo, Y. Feng, X. Xiao, D. Gee, J. Sleasman, M. Goodenow, R. Biggar, and D. Dimitrov (1999)
Blood 93, 2824-2830
   Abstract »    Full Text »    PDF »
Virus-Induced CD8+ T Cell Clonal Expansion Is Associated with Telomerase Up-Regulation and Telomere Length Preservation: A Mechanism for Rescue from Replicative Senescence.
M. K. Maini, M. V. D. Soares, C. F. Zilch, A. N. Akbar, and P. C. L. Beverley (1999)
J. Immunol. 162, 4521-4526
   Abstract »    Full Text »    PDF »
Normal T-Cell Telomerase Activity and Upregulation in Human Immunodeficiency Virus-1 Infection.
K. C. Wolthers, S. A. Otto, G. B. A. Wisman, S. Fleury, P. Reiss, R. W. ten Kate, A. G.J. van der Zee, and F. Miedema (1999)
Blood 93, 1011-1019
   Abstract »    Full Text »    PDF »
Asymptomatic Simian Immunodeficiency Virus Infection Decreases Blood CD4+ T Cells by Accumulating Recirculating Lymphocytes in the Lymphoid Tissues.
A. R. Schenkel, H. Uno, and C. D. Pauza (1999)
J. Virol. 73, 601-607
   Abstract »    Full Text »    PDF »
T Cell Renewal Rates, Telomerase, and Telomere Length Shortening.
R. J. De Boer and A. J. Noest (1998)
J. Immunol. 160, 5832-5837
   Abstract »    Full Text »    PDF »
The Effect of Deletion of the V3 Loop of gp120 on Cytotoxic T Cell Responses and HIV gp120-Mediated Pathogenesis.
D. Kmieciak, T. J. Wasik, H. Teppler, J. Pientka, S. H. Hsu, H. Takahashi, K. Okumura, Y. Kaneko, and D. Kozbor (1998)
J. Immunol. 160, 5676-5683
   Abstract »    Full Text »    PDF »
Increased rates of CD4+ and CD8+ T lymphocyte turnover in simian immunodeficiency virus-infected macaques.
M. Rosenzweig, M. DeMaria, D. M. Harper, S. Friedrich, R. K. Jain, and R. P. Johnson (1998)
PNAS 95, 6388-6393
   Abstract »    Full Text »    PDF »
Turnover of CD4+ and CD8+ T Lymphocytes in HIV-1 Infection as Measured by Ki-67 Antigen.
N. Sachsenberg, A. S. Perelson, S. Yerly, G. A. Schockmel, D. Leduc, B. Hirschel, and L. Perrin (1998)
J. Exp. Med. 187, 1295-1303
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus-1 Infection Interrupts Thymopoiesis and Multilineage Hematopoiesis In Vivo.
M. Jenkins, M. B. Hanley, M. B. Moreno, E. Wieder, and J. M. McCune (1998)
Blood 91, 2672-2678
   Abstract »    Full Text »    PDF »
Interferon alpha  and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS.
D. Zagury, A. Lachgar, V. Chams, L. S. Fall, J. Bernard, J.-F. Zagury, B. Bizzini, A. Gringeri, E. Santagostino, J. Rappaport, et al. (1998)
PNAS 95, 3851-3856
   Abstract »    Full Text »    PDF »
The Unenlarged Lymph Nodes of HIV-1-infected, Asymptomatic Patients with High CD4 T Cell Counts Are Sites for Virus Replication and CD4 T Cell Proliferation. The Impact of Highly Active Antiretroviral Therapy.
K. Tenner-Racz, H.-J. Stellbrink, J. van Lunzen, C. Schneider, J.-P. Jacobs, B. Raschdorff, G. Grossschupff, R. M. Steinman, and P. Racz (1998)
J. Exp. Med. 187, 949-959
   Abstract »    Full Text »    PDF »
Rapid Turnover of T Lymphocytes in SIV-Infected Rhesus Macaques.
H. Mohri, S. Bonhoeffer, S. Monard, A. S. Perelson, and D. D. Ho (1998)
Science 279, 1223-1227
   Abstract »    Full Text »
Measurement of cell proliferation by labeling of DNA with stable isotope-labeled glucose: Studies in vitro, in animals, and in humans.
D. C. Macallan, C. A. Fullerton, R. A. Neese, K. Haddock, S. S. Park, and M. K. Hellerstein (1998)
PNAS 95, 708-713
   Abstract »    Full Text »    PDF »
Positive Effects of Combined Antiretroviral Therapy on CD4+ T Cell Homeostasis and Function in Advanced HIV Disease.
B. Autran, G. Carcelain, T. S. Li, C. Blanc, D. Mathez, R. Tubiana, C. Katlama, P. Debré, and J. Leibowitch (1997)
Science 277, 112-116
   Abstract »    Full Text »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)