Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 222K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Badley, A. D. Articles by Paya, C. V. Search for Related Content PubMed PubMed Citation Articles by Badley, A. D. Articles by Paya, C. V. Social Bookmarking                            What's this?

Articles

Andrew D. Badley^*, David Dockrell^*, Margaret Simpson, Ron Schut, David H. Lynch, Paul Leibson^||, and Carlos V. Paya^¶,*,||

From the ^* Division of Infectious Diseases, ^¶ Division of Experimental Pathology, and ^|| Department of Immunology, Mayo Clinic, Rochester, Minnesota 55901; Division of Infectious Diseases, Hennepin County Medical Center, Minneapolis, Minnesota 55404; and Immunex Corporation, Seattle, Washington 98101

Apoptosis of bystander uninfected CD4⁺ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4⁺ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4⁺, but not CD8⁺ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4⁺ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4⁺ T cells in HIV-infected individuals.

We would like to acknowledge the excellent secretarial assistance of Mr. Douglas Hauschild.

Drs. Badley and Dockrell contributed equally to this work.

¹Abbreviation used in this paper: MDM, monocyte derived macrophage.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Hanna, Z., Priceputu, E., Chrobak, P., Hu, C., Dugas, V., Goupil, M., Marquis, M., de Repentigny, L., Jolicoeur, P. (2009). Selective Expression of Human Immunodeficiency Virus Nef in Specific Immune Cell Populations of Transgenic Mice Is Associated with Distinct AIDS-Like Phenotypes. J. Virol. 83: 9743-9758 [Abstract] [Full Text]  
• Aquaro, S., Svicher, V., Schols, D., Pollicita, M., Antinori, A., Balzarini, J., Perno, C. F. (2006). Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: new therapeutic strategies. J. Leukoc. Biol. 80: 1103-1110 [Abstract] [Full Text]  
• Roeth, J. F., Collins, K. L. (2006). Human Immunodeficiency Virus Type 1 Nef: Adapting to Intracellular Trafficking Pathways. Microbiol. Mol. Biol. Rev. 70: 548-563 [Abstract] [Full Text]  
• Papasavvas, E., Sun, J., Luo, Q., Moore, E. C., Thiel, B., MacGregor, R. R., Minty, A., Mounzer, K., Kostman, J. R., Montaner, L. J. (2005). IL-13 Acutely Augments HIV-Specific and Recall Responses from HIV-1-Infected Subjects In Vitro by Modulating Monocytes. J. Immunol. 175: 5532-5540 [Abstract] [Full Text]  
• Aquaro, S., Svicher, V., Ceccherini-Silberstein, F., Cenci, A., Marcuccilli, F., Giannella, S., Marcon, L., Calio, R., Balzarini, J., Perno, C.-F. (2005). Limited development and progression of resistance of HIV-1 to the nucleoside analogue reverse transcriptase inhibitor lamivudine in human primary macrophages. J Antimicrob Chemother 55: 872-878 [Abstract] [Full Text]  
• Priceputu, E., Rodrigue, I., Chrobak, P., Poudrier, J., Mak, T. W., Hanna, Z., Hu, C., Kay, D. G., Jolicoeur, P. (2005). The Nef-Mediated AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Increased Fas/FasL Expression on T Cells and T-Cell Death but Is Not Prevented in Fas-, FasL-, Tumor Necrosis Factor Receptor 1-, or Interleukin-1{beta}-Converting Enzyme-Deficient or Bcl2-Expressing Transgenic Mice. J. Virol. 79: 6377-6391 [Abstract] [Full Text]  
• Herbeuval, J.-P., Boasso, A., Grivel, J.-C., Hardy, A. W., Anderson, S. A., Dolan, M. J., Chougnet, C., Lifson, J. D., Shearer, G. M. (2005). TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells. Blood 105: 2458-2464 [Abstract] [Full Text]  
• Wang, W.-H., Gregori, G., Hullinger, R. L., Andrisani, O. M. (2004). Sustained Activation of p38 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase Pathways by Hepatitis B Virus X Protein Mediates Apoptosis via Induction of Fas/FasL and Tumor Necrosis Factor (TNF) Receptor 1/TNF-{alpha} Expression. Mol. Cell. Biol. 24: 10352-10365 [Abstract] [Full Text]  
• De Rose, V., Cappello, P., Sorbello, V., Ceccarini, B., Gani, F., Bosticardo, M., Fassio, S., Novelli, F. (2004). IFN-{gamma} inhibits the proliferation of allergen-activated T lymphocytes from atopic, asthmatic patients by inducing Fas/FasL-mediated apoptosis. J. Leukoc. Biol. 76: 423-432 [Abstract] [Full Text]  
• Decrion, A.-Z., Varin, A., Estavoyer, J.-M., Herbein, G. (2004). CXCR4-mediated T cell apoptosis in human immunodeficiency virus infection. J. Gen. Virol. 85: 1471-1478 [Abstract] [Full Text]  
• Holm, G. H., Zhang, C., Gorry, P. R., Peden, K., Schols, D., De Clercq, E., Gabuzda, D. (2004). Apoptosis of Bystander T Cells Induced by Human Immunodeficiency Virus Type 1 with Increased Envelope/Receptor Affinity and Coreceptor Binding Site Exposure. J. Virol. 78: 4541-4551 [Abstract] [Full Text]  
• Garaci, E., Aquaro, S., Lapenta, C., Amendola, A., Spada, M., Covaceuszach, S., Perno, C.-F., Belardelli, F. (2003). Anti-nerve growth factor Ab abrogates macrophage-mediated HIV-1 infection and depletion of CD4+ T lymphocytes in hu-SCID mice. Proc. Natl. Acad. Sci. USA 100: 8927-8932 [Abstract] [Full Text]  
• Jekle, A., Keppler, O. T., De Clercq, E., Schols, D., Weinstein, M., Goldsmith, M. A. (2003). In Vivo Evolution of Human Immunodeficiency Virus Type 1 toward Increased Pathogenicity through CXCR4-Mediated Killing of Uninfected CD4 T Cells. J. Virol. 77: 5846-5854 [Abstract] [Full Text]  
• Mor, G., Sapi, E., Abrahams, V. M., Rutherford, T., Song, J., Hao, X.-Y., Muzaffar, S., Kohen, F. (2003). Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes. J. Immunol. 170: 114-122 [Abstract] [Full Text]  
• Epelman, S., Neely, G. G., Ma, L. L., Gjomarkaj, M., Pace, E., Melis, M., Woods, D. E., Mody, C. H. (2002). Distinct fates of monocytes and T cells directly activated by Pseudomonas aeruginosa exoenzyme S. J. Leukoc. Biol. 71: 458-468 [Abstract] [Full Text]  
• de Oliveira Pinto, L. M., Garcia, S., Lecoeur, H., Rapp, C., Gougeon, M.-L. (2002). Increased sensitivity of T lymphocytes to tumor necrosis factor receptor 1 (TNFR1)- and TNFR2-mediated apoptosis in HIV infection: relation to expression of Bcl-2 and active caspase-8 and caspase-3. Blood 99: 1666-1675 [Abstract] [Full Text]  
• Lu, G., Janjic, B. M., Janjic, J., Whiteside, T. L., Storkus, W. J., Vujanovic, N. L. (2002). Innate Direct Anticancer Effector Function of Human Immature Dendritic Cells. II. Role of TNF, Lymphotoxin-{alpha}1{beta}2, Fas Ligand, and TNF-Related Apoptosis-Inducing Ligand. J. Immunol. 168: 1831-1839 [Abstract] [Full Text]  
• Lu, W., Achour, A., Arlie, M., Cao, L., Andrieu, J.-M. (2001). Enhanced Dendritic Cell-Driven Proliferation and Anti-HIV Activity of CD8+ T Cells by a New Phenothiazine Derivative, Aminoperazine. J. Immunol. 167: 2929-2935 [Abstract] [Full Text]  
• Roggero, R., Robert-Hebmann, V., Harrington, S., Roland, J., Vergne, L., Jaleco, S., Devaux, C., Biard-Piechaczyk, M. (2001). Binding of Human Immunodeficiency Virus Type 1 gp120 to CXCR4 Induces Mitochondrial Transmembrane Depolarization and Cytochrome c-Mediated Apoptosis Independently of Fas Signaling. J. Virol. 75: 7637-7650 [Abstract] [Full Text]  
• Shi, J., Gilbert, G. E., Kokubo, Y., Ohashi, T. (2001). Role of the liver in regulating numbers of circulating neutrophils. Blood 98: 1226-1230 [Abstract] [Full Text]  
• Lane, B. R., Strieter, R. M., Coffey, M. J., Markovitz, D. M. (2001). Human Immunodeficiency Virus Type 1 (HIV-1)-Induced GRO-{alpha} Production Stimulates HIV-1 Replication in Macrophages and T Lymphocytes. J. Virol. 75: 5812-5822 [Abstract] [Full Text]  
• Nwakoby, I. E., Reddy, K., Patel, P., Shah, N., Sharma, S., Bhaskaran, M., Gibbons, N., Kapasi, A. A., Singhal, P. C. (2001). Fas-Mediated Apoptosis of Neutrophils in Sera of Patients with Infection. Infect. Immun. 69: 3343-3349 [Abstract] [Full Text]  
• Dzialo-Hatton, R., Milbrandt, J., Hockett, R. D. Jr., Weaver, C. T. (2001). Differential Expression of Fas Ligand in Th1 and Th2 Cells Is Regulated by Early Growth Response Gene and NF-AT Family Members. J. Immunol. 166: 4534-4542 [Abstract] [Full Text]  
• Cannavo', G., Paiardini, M., Galati, D., Cervasi, B., Montroni, M., De Vico, G., Guetard, D., Bocchino, M. L., Picerno, I., Magnani, M., Silvestri, G., Piedimonte, G. (2001). Abnormal intracellular kinetics of cell-cycle-dependent proteins in lymphocytes from patients infected with human immunodeficiency virus: a novel biologic link between immune activation, accelerated T-cell turnover, and high levels of apoptosis. Blood 97: 1756-1764 [Abstract] [Full Text]  
• Kamradt, T., Mitchison, N. A. (2001). Tolerance and Autoimmunity. NEJM 344: 655-664 [Full Text]  
• AGOSTINI, C., SIVIERO, M., FACCO, M., CAROLLO, D., BINOTTO, G., TOSONI, A., CATTELAN, A. M., ZAMBELLO, R., TRENTIN, L., SEMENZATO, G. (2001). Antiapoptotic Effects of IL-15 on Pulmonary Tc1 Cells of Patients with Human Immunodeficiency Virus Infection. Am. J. Respir. Crit. Care Med. 163: 484-489 [Abstract] [Full Text]  
• Mahlknecht, U., Deng, C., Lu, M. C., Greenough, T. C., Sullivan, J. L., O'Brien, W. A., Herbein, G. (2000). Resistance to Apoptosis in HIV-Infected CD4+ T Lymphocytes Is Mediated by Macrophages: Role for Nef and Immune Activation in Viral Persistence. J. Immunol. 165: 6437-6446 [Abstract] [Full Text]  
• Badley, A. D., Pilon, A. A., Landay, A., Lynch, D. H. (2000). Mechanisms of HIV-associated lymphocyte apoptosis. Blood 96: 2951-2964 [Abstract] [Full Text]  
• Aquaro, S., Panti, S., Caroleo, M. C., Balestra, E., Cenci, A., Forbici, F., Ippolito, G., Mastino, A., Testi, R., Mollace, V., Calio, R., Perno, C. F. (2000). Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes. J. Leukoc. Biol. 68: 429-435 [Abstract] [Full Text]  
• Darcissac, E. C. A., Truong, M.-J., Dewulf, J., Mouton, Y., Capron, A., Bahr, G. M. (2000). The Synthetic Immunomodulator Murabutide Controls Human Immunodeficiency Virus Type 1 Replication at Multiple Levels in Macrophages and Dendritic Cells. J. Virol. 74: 7794-7802 [Abstract] [Full Text]  
• Epelman, S., Bruno, T. F., Neely, G. G., Woods, D. E., Mody, C. H. (2000). Pseudomonas aeruginosa Exoenzyme S Induces Transcriptional Expression of Proinflammatory Cytokines and Chemokines. Infect. Immun. 68: 4811-4814 [Abstract] [Full Text]  
• Kremer, L., Estaquier, J., Wolowczuk, I., Biet, F., Ameisen, J.-C., Locht, C. (2000). Ineffective Cellular Immune Response Associated with T-Cell Apoptosis in Susceptible Mycobacterium bovis BCG-Infected Mice. Infect. Immun. 68: 4264-4273 [Abstract] [Full Text]  
• Tateyama, M., Oyaizu, N., McCloskey, T. W., Than, S., Pahwa, S. (2000). 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. Blood 96: 195-202 [Abstract] [Full Text]  
• Somma, F., Tuosto, L., Montani, M. S. G., Di Somma, M. M., Cundari, E., Piccolella, E. (2000). Engagement of CD4 Before TCR Triggering Regulates Both Bax- and Fas (CD95)-Mediated. J. Immunol. 164: 5078-5087 [Abstract] [Full Text]  
• Herbein, G., O'brien, W. A. (2000). Tumor Necrosis Factor (TNF)-{alpha} and TNF Receptors in Viral Pathogenesis. Exp. Biol. Med. 223: 241-257 [Abstract] [Full Text]  
• Duffield, J. S., Erwig, L.-P., Wei, X.-q., Liew, F. Y., Rees, A. J., Savill, J. S. (2000). Activated Macrophages Direct Apoptosis and Suppress Mitosis of Mesangial Cells. J. Immunol. 164: 2110-2119 [Abstract] [Full Text]  
• Shankar, P., Xu, Z., Lieberman, J. (1999). Viral-Specific Cytotoxic T Lymphocytes Lyse Human Immunodeficiency Virus-Infected Primary T Lymphocytes by the Granule Exocytosis Pathway. Blood 94: 3084-3093 [Abstract] [Full Text]  
• Bohler, T., Debatin, K.-M., Linde;, R., Pahwa, S., McCloskey, T. W. (1999). Sensitivity of CD4+ Peripheral Blood T Cells Toward Spontaneous and CD95 (APO-1/Fas)-Induced Apoptosis in Pediatric Human Immunodeficiency Virus Infection. Blood 94: 1829-1833 [Full Text]  
• Hadida, F., Vieillard, V., Mollet, L., Clark-Lewis, I., Baggiolini, M., Debre, P. (1999). Cutting Edge: RANTES Regulates Fas Ligand Expression and Killing by HIV-Specific CD8 Cytotoxic T Cells. J. Immunol. 163: 1105-1109 [Abstract] [Full Text]  
• Singh, R. K., Varney, M. L., Buyukberber, S., Ino, K., Ageitos, A. G., Reed, E., Tarantolo, S., Talmadge, J. E. (1999). Fas-FasL-mediated CD4+ T-Cell Apoptosis following Stem Cell Transplantation. Cancer Res. 59: 3107-3111 [Abstract] [Full Text]  
• Bailer, R. T., Holloway, A., Sun, J., Margolick, J. B., Martin, M., Kostman, J., Montaner, L. J. (1999). IL-13 and IFN-{gamma} Secretion by Activated T Cells in HIV-1 Infection Associated with Viral Suppression and a Lack of Disease Progression. J. Immunol. 162: 7534-7542 [Abstract] [Full Text]  
• Yin, C., Wu, M. S., Pauza, C. D., Salvato, M. S. (1999). High Major Histocompatibility Complex-Unrestricted Lysis of Simian Immunodeficiency Virus Envelope-Expressing Cells Predisposes Macaques to Rapid AIDS Progression. J. Virol. 73: 3692-3701 [Abstract] [Full Text]  
• Griffith, T. S., Wiley, S. R., Kubin, M. Z., Sedger, L. M., Maliszewski, C. R., Fanger, N. A. (1999). Monocyte-mediated Tumoricidal Activity via the Tumor Necrosis Factor-related Cytokine, TRAIL. JEM 189: 1343-1354 [Abstract] [Full Text]  
• Gómez del Moral, M., Ortuño, E., Fernández-Zapatero, P., Alonso, F., Alonso, C., Ezquerra, A., Domínguez, J. (1999). African Swine Fever Virus Infection Induces Tumor Necrosis Factor Alpha Production: Implications in Pathogenesis. J. Virol. 73: 2173-2180 [Abstract] [Full Text]  
• Van Hoffen, E., Van Wichen, D. F., Leemans, J. C., Broekhuizen, R. A.J.F., Bruggink, A. H., De Boer, M., De Jonge, N., Kirkels, H., Slootweg, P. J., Gmelig-Meyling, F. H.J., De Weger, R. A. (1998). T Cell Apoptosis in Human Heart Allografts : Association with Lack of Co-Stimulation?. Am. J. Pathol. 153: 1813-1824 [Abstract] [Full Text]  
• McCloskey, T. W., Bakshi, S., Than, S., Arman, P., Pahwa, S. (1998). Immunophenotypic Analysis of Peripheral Blood Mononuclear Cells Undergoing In Vitro Apoptosis After Isolation From Human Immunodeficiency Virus-Infected Children. Blood 92: 4230-4237 [Abstract] [Full Text]  
• Davis, I. C., Girard, M., Fultz, P. N. (1998). Loss of CD4+ T Cells in Human Immunodeficiency Virus Type 1-Infected Chimpanzees Is Associated with Increased Lymphocyte Apoptosis. J. Virol. 72: 4623-4632 [Abstract] [Full Text]  
• Algeciras, A., Dockrell, D. H., Lynch, D. H., Paya, C. V. (1998). CD4 Regulates Susceptibility to Fas ligand- and Tumor Necrosis Factor-mediated Apoptosis. JEM 187: 711-720 [Abstract] [Full Text]  
• Holtz-Heppelmann, C. J., Algeciras, A., Badley, A. D., Paya, C. V. (1998). Transcriptional Regulation of the Human FasL Promoter-Enhancer Region. J. Biol. Chem. 273: 4416-4423 [Abstract] [Full Text]  
• Ferrante, P., Fusi, M. L., Saresella, M., Caputo, D., Biasin, M., Trabattoni, D., Salvaggio, A., Clerici, E., de Vries, J. E., Aversa, G., Cazzullo, C. L., Clerici, M. (1998). Cytokine Production and Surface Marker Expression in Acute and Stable Multiple Sclerosis: Altered IL-12 Production and Augmented Signaling Lymphocytic Activation Molecule (SLAM)-Expressing Lymphocytes in Acute Multiple Sclerosis. J. Immunol. 160: 1514-1521 [Abstract] [Full Text]  
• Herbein, G., Van Lint, C., Lovett, J. L., Verdin, E. (1998). Distinct Mechanisms Trigger Apoptosis in Human Immunodeficiency Virus Type 1-Infected and in Uninfected Bystander T Lymphocytes. J. Virol. 72: 660-670 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS