| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Clinical Immunology Unit/Institute of Molecular Medicine, Faculty of Medicine of Lisbon, Lisbon, Portugal;
Instituto Gulbenkian de Ciência, Oeiras, Portugal;
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
The causal relationships among CD4 cell depletion, HIV replication, and immune activation are not well understood. HIV-2 infection, "nature’s experiment" with inherently attenuated HIV disease, provides additional insights into this issue. We report the finding that in HIV-2 and HIV-1 patients with a comparable degree of CD4 depletion the imbalance in the relative sizes of the naive and memory T cell populations and the up-regulation of CD4 and CD8 cell activation markers (HLA-DR, CD38, CD69, Fas molecules) are similar, even though the viral load in the plasma of HIV-2-infected patients is two orders of magnitude lower than in HIV-1 patients and HIV-2 patients are known to have slower rates of CD4 T cell decline and a better clinical prognosis. Moreover, we found a similar increase in the frequency of cycling CD4 T cells (Ki67+), which was in strong correlation with the expression of activation markers. Finally, the level of T cell anergy, as assessed by the proliferative responses to CD3 stimulation and to a panel of microbial Ags, proved to be comparable in HIV-1 and HIV-2 patients with a similar degree of CD4 depletion despite large differences in viral load. Our data are consistent with a direct causal relationship between immune activation and CD4 cell depletion in HIV disease and an only indirect relation of these parameters to the virus replication rate. Invoking the concept of proximal immune activation and virus transmission, which links efficient transmission of virus to local cell activation and proliferation in response to Ags and inflammation, we propose an integrative interpretation of the data and suggest that strongly elevated immune activation induces CD4 cell depletion and not vice versa, with potential implications for the choice of treatment strategies.
This article has been cited by other articles:
|
|
 |
|
  I. Pandrea, R. Onanga, S. Souquiere, A. Mouinga-Ondeme, O. Bourry, M. Makuwa, P. Rouquet, G. Silvestri, F. Simon, P. Roques, et al. Paucity of CD4+ CCR5+ T Cells May Prevent Transmission of Simian Immunodeficiency Virus in Natural Nonhuman Primate Hosts by Breast-Feeding J. Virol., June 1, 2008; 82(11): 5501 - 5509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Dunham, B. Cervasi, J. M. Brenchley, H. Albrecht, A. Weintrob, B. Sumpter, J. Engram, S. Gordon, N. R. Klatt, I. Frank, et al. CD127 and CD25 Expression Defines CD4+ T Cell Subsets That Are Differentially Depleted during HIV Infection J. Immunol., April 15, 2008; 180(8): 5582 - 5592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Pandrea, R. M. Ribeiro, R. Gautam, T. Gaufin, M. Pattison, M. Barnes, C. Monjure, C. Stoulig, J. Dufour, W. Cyprian, et al. Simian Immunodeficiency Virus SIVagm Dynamics in African Green Monkeys J. Virol., April 1, 2008; 82(7): 3713 - 3724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Sedaghat, J. German, T. M. Teslovich, J. Cofrancesco Jr., C. C. Jie, C. C. Talbot Jr., and R. F. Siliciano Chronic CD4+ T-Cell Activation and Depletion in Human Immunodeficiency Virus Type 1 Infection: Type I Interferon-Mediated Disruption of T-Cell Dynamics J. Virol., February 15, 2008; 82(4): 1870 - 1883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Ndhlovu, C. P. Loo, G. Spotts, D. F. Nixon, and F. M. Hecht FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection J. Leukoc. Biol., February 1, 2008; 83(2): 254 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Gautier, S. Beq, C. S. Cortesao, A. E. Sousa, and R. Cheynier Efficient Thymopoiesis Contributes to the Maintenance of Peripheral CD4 T Cells during Chronic Human Immunodeficiency Virus Type 2 Infection J. Virol., November 15, 2007; 81(22): 12685 - 12688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. V. Pandrea, R. Gautam, R. M. Ribeiro, J. M. Brenchley, I. F. Butler, M. Pattison, T. Rasmussen, P. A. Marx, G. Silvestri, A. A. Lackner, et al. Acute Loss of Intestinal CD4+ T Cells Is Not Predictive of Simian Immunodeficiency Virus Virulence J. Immunol., September 1, 2007; 179(5): 3035 - 3046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Albuquerque, C. S. Cortesao, R. B. Foxall, R. S. Soares, R. M. M. Victorino, and A. E. Sousa Rate of Increase in Circulating IL-7 and Loss of IL-7R{alpha} Expression Differ in HIV-1 and HIV-2 Infections: Two Lymphopenic Diseases with Similar Hyperimmune Activation but Distinct Outcomes J. Immunol., March 1, 2007; 178(5): 3252 - 3259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rodriguez, M. M. Lederman, A. K. Sethi, V. K. Cheruvu, R. J. Bosch, J. Martin, and S. Deeks Presenting Plasma HIV RNA Level and Rate of CD4 T-Cell Decline--Reply JAMA, February 28, 2007; 297(8): 806 - 807. [Full Text] [PDF]
|
|
|
|
 |
|
 I. Pandrea, C. Apetrei, S. Gordon, J. Barbercheck, J. Dufour, R. Bohm, B. Sumpter, P. Roques, P. A. Marx, V. M. Hirsch, et al. Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts Blood, February 1, 2007; 109(3): 1069 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Soares, R. Foxall, A. Albuquerque, C. Cortesao, M. Garcia, R. M. M. Victorino, and A. E. Sousa Increased Frequency of Circulating CCR5+ CD4+ T Cells in Human Immunodeficiency Virus Type 2 Infection J. Virol., December 15, 2006; 80(24): 12425 - 12429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Cervasi, M. Paiardini, S. Serafini, A. Fraternale, M. Menotta, J. Engram, B. Lawson, S. I. Staprans, G. Piedimonte, C. F. Perno, et al. Administration of Fludarabine-Loaded Autologous Red Blood Cells in Simian Immunodeficiency Virus-Infected Sooty Mangabeys Depletes pSTAT-1-Expressing Macrophages and Delays the Rebound of Viremia after Suspension of Antiretroviral Therapy. J. Virol., November 1, 2006; 80(21): 10335 - 10345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Epple, C. Loddenkemper, D. Kunkel, H. Troger, J. Maul, V. Moos, E. Berg, R. Ullrich, J.-D. Schulzke, H. Stein, et al. Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART Blood, November 1, 2006; 108(9): 3072 - 3078. [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]
|
|
|
|
|
|
M. Di Mascio, I. Sereti, L. T. Matthews, V. Natarajan, J. Adelsberger, R. Lempicki, C. Yoder, E. Jones, C. Chow, J. A. Metcalf, et al. Naive T-Cell Dynamics in Human Immunodeficiency Virus Type 1 Infection: Effects of Highly Active Antiretroviral Therapy Provide Insights into the Mechanisms of Naive T-Cell Depletion J. Virol., March 15, 2006; 80(6): 2665 - 2674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Wang, B. Metcalf, R. M. Ribeiro, H. McClure, and A. Kaur Th-1-Type Cytotoxic CD8+ T-Lymphocyte Responses to Simian Immunodeficiency Virus (SIV) Are a Consistent Feature of Natural SIV Infection in Sooty Mangabeys J. Virol., March 15, 2006; 80(6): 2771 - 2783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Marchant, S. J. D. Neil, and A. McKnight Human immunodeficiency virus types 1 and 2 have different replication kinetics in human primary macrophage culture J. Gen. Virol., February 1, 2006; 87(2): 411 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Paiardini, B. Cervasi, B. Sumpter, H. M. McClure, D. L. Sodora, M. Magnani, S. I. Staprans, G. Piedimonte, and G. Silvestri Perturbations of Cell Cycle Control in T Cells Contribute to the Different Outcomes of Simian Immunodeficiency Virus Infection in Rhesus Macaques and Sooty Mangabeys J. Virol., January 15, 2006; 80(2): 634 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. EGGENA, H. HOPKINS, B. BARUGAHARE, M. OKELLO, F. SSALI, P. MUGYENYI, P. J. ROSENTHAL, H. CAO, and G. DORSEY CD4 T CELL ACTIVATION AS A PREDICTOR FOR TREATMENT FAILURE IN UGANDANS WITH PLASMODIUM FALCIPARUM MALARIA Am J Trop Med Hyg, January 1, 2006; 74(1): 41 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Muthukumar, D. Zhou, M. Paiardini, A. P. Barry, K. S. Cole, H. M. McClure, S. I. Staprans, G. Silvestri, and D. L. Sodora Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys Blood, December 1, 2005; 106(12): 3839 - 3845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Peretz, G. Alter, M.-P. Boisvert, G. Hatzakis, C. M. Tsoukas, and N. F. Bernard Human Immunodeficiency Virus (HIV)-Specific Gamma Interferon Secretion Directed against All Expressed HIV Genes: Relationship to Rate of CD4 Decline J. Virol., April 15, 2005; 79(8): 4908 - 4917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Silvestri, A. Fedanov, S. Germon, N. Kozyr, W. J. Kaiser, D. A. Garber, H. McClure, M. B. Feinberg, and S. I. Staprans Divergent Host Responses during Primary Simian Immunodeficiency Virus SIVsm Infection of Natural Sooty Mangabey and Nonnatural Rhesus Macaque Hosts J. Virol., April 1, 2005; 79(7): 4043 - 4054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Eggena, B. Barugahare, N. Jones, M. Okello, S. Mutalya, C. Kityo, P. Mugyenyi, and H. Cao Depletion of Regulatory T Cells in HIV Infection Is Associated with Immune Activation J. Immunol., April 1, 2005; 174(7): 4407 - 4414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Paiardini, B. Cervasi, H. Albrecht, A. Muthukumar, R. Dunham, S. Gordon, H. Radziewicz, G. Piedimonte, M. Magnani, M. Montroni, et al. Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals J. Immunol., March 1, 2005; 174(5): 2900 - 2909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Borkow and Z. Bentwich Chronic Immune Activation Associated with Chronic Helminthic and Human Immunodeficiency Virus Infections: Role of Hyporesponsiveness and Anergy Clin. Microbiol. Rev., October 1, 2004; 17(4): 1012 - 1030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Doisne, A. Urrutia, C. Lacabaratz-Porret, C. Goujard, L. Meyer, M.-L. Chaix, M. Sinet, and A. Venet CD8+ T Cells Specific for EBV, Cytomegalovirus, and Influenza Virus Are Activated during Primary HIV Infection J. Immunol., August 15, 2004; 173(4): 2410 - 2418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Deeks, C. M. R. Kitchen, L. Liu, H. Guo, R. Gascon, A. B. Narvaez, P. Hunt, J. N. Martin, J. O. Kahn, J. Levy, et al. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load Blood, August 15, 2004; 104(4): 942 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Sereti, K. B. Anthony, H. Martinez-Wilson, R. Lempicki, J. Adelsberger, J. A. Metcalf, C. W. Hallahan, D. Follmann, R. T. Davey, J. A. Kovacs, et al. IL-2-induced CD4+ T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation Blood, August 1, 2004; 104(3): 775 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Bahbouhi, A. Landay, and L. Al-Harthi Dynamics of cytokine expression in HIV productively infected primary CD4+ T cells Blood, June 15, 2004; 103(12): 4581 - 4587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Vahlenkamp, M. B. Tompkins, and W. A. F. Tompkins Feline Immunodeficiency Virus Infection Phenotypically and Functionally Activates Immunosuppressive CD4+CD25+ T Regulatory Cells J. Immunol., April 15, 2004; 172(8): 4752 - 4761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Schattner, J. Friedman, and Z. Bentwich Opportunistic infection due to unexplained CD4+ lymphocytopenia and associated Sjogren's syndrome Rheumatology, January 1, 2004; 43(1): 111 - 112. [Full Text] [PDF]
|
|
|
|
 |
|
 S.-A. Younes, B. Yassine-Diab, A. R. Dumont, M.-R. Boulassel, Z. Grossman, J.-P. Routy, and R.-P. Sekaly HIV-1 Viremia Prevents the Establishment of Interleukin 2-producing HIV-specific Memory CD4+ T Cells Endowed with Proliferative Capacity J. Exp. Med., December 15, 2003; 198(12): 1909 - 1922. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
