Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics

doi:10.1084/jem.181.4.1365

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Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics

MR Klein, CA van Baalen, AM Holwerda, SR Kerkhof Garde, RJ Bende, IP Keet, JK Eeftinck-Schattenkerk, AD Osterhaus, H Schuitemaker and F Miedema
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.

To gain more insight into the role of HIV-1-specific cytotoxic T lymphocytes (CTL) in the pathogenesis of AIDS, we investigated temporal relations between HIV-1 Gag-specific precursor CTL (CTLp), HIV-1 viral load, CD4+ T cell counts, and T cell function. Six HIV-1-infected subjects, who were asymptomatic for more than 8 yr with CD4+ counts > 500 cells/mm3, were compared with six subjects who progressed to AIDS within 5 yr after HIV-1 seroconversion. In the long-term asymptomatics, persistent HIV-1 Gag-specific CTL responses and very low numbers of HIV- 1-infected CD4+ T cells coincided with normal and stable CD4+ counts and preserved CD3 mAb-induced T cell reactivity for more than 8 yr. In five out of six rapid progressors Gag-specific CTLp were also detected. However, early in infection the number of circulating HIV-1-infected CD4+ T cells increased despite strong and mounting Gag-specific CTL responses. During subsequent clinical progression to AIDS, loss of Gag- specific CTLp coincided with precipitating CD4+ counts and severe deterioration of T cell function. The possible relationships of HIV-1 Gag-specific CTLp to disease progression are discussed.
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Huang, Y., Kong, W.-p., Nabel, G. J. (2001). Human Immunodeficiency Virus Type 1-Specific Immunity after Genetic Immunization Is Enhanced by Modification of Gag and Pol Expression. J. Virol. 75: 4947-4951 [Abstract] [Full Text]
Fan, Z., Huang, X.-L., Borowski, L., Mellors, J. W., Rinaldo, C. R. Jr. (2001). Restoration of Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Responses in CD8+ T Cells from Late-Stage Patients on Prolonged Antiretroviral Therapy by Stimulation In Vitro with HIV-1 Protein-Loaded Dendritic Cells. J. Virol. 75: 4413-4419 [Abstract] [Full Text]
Hogan, C. M., Hammer, S. M. (2001). Host Determinants in HIV Infection and Disease: Part 1: Cellular and Humoral Immune Responses. ANN INTERN MED 134: 761-776 [Abstract] [Full Text]
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Hladik, F., Bender, S., Akridge, R. E., Hu, Y., Galloway, C., Francis, D., McElrath, M. J. (2001). Recombinant HIV-1 Glycoprotein 120 Induces Distinct Types of Delayed Hypersensitivity in Persons With or Without Pre-Existing Immunologic Memory. J. Immunol. 166: 3580-3588 [Abstract] [Full Text]
Ciurea, A., Hunziker, L., Klenerman, P., Hengartner, H., Zinkernagel, R. M. (2001). Impairment of Cd4+ T Cell Responses during Chronic Virus Infection Prevents Neutralizing Antibody Responses against Virus Escape Mutants. JEM 193: 297-306 [Abstract] [Full Text]
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Goulder, P. J.R., Altfeld, M. A., Rosenberg, E. S., Nguyen, T., Tang, Y., Eldridge, R. L., Addo, M. M., He, S., Muckerjee, J. S., Phillips, M. N., Bunce, M., Kalams, S. A., Sekaly, R. P., Walker, B. D., Brander, C. (2001). Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection. JEM 193: 181-194 [Abstract] [Full Text]
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Chun, T.-W., Justement, J. S., Moir, S., Hallahan, C. W., Ehler, L. A., Liu, S., McLaughlin, M., Dybul, M., Mican, J. M., Fauci, A. S. (2001). Suppression of HIV replication in the resting CD4+ T cell reservoir by autologous CD8+ T cells: Implications for the development of therapeutic strategies. Proc. Natl. Acad. Sci. USA 98: 253-258 [Abstract] [Full Text]
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Lori, F., Lewis, M. G., Xu, J., Varga, G., Zinn Jr., D. E., Crabbs, C., Wagner, W., Greenhouse, J., Silvera, P., Yalley-Ogunro, J., Tinelli, C., Lisziewicz, J. (2000). Control of SIV Rebound Through Structured Treatment Interruptions During Early Infection. Science 290: 1591-1593 [Abstract] [Full Text]
Goepfert, P. A., Bansal, A., Edwards, B. H., Ritter, G. D. Jr., Tellez, I., McPherson, S. A., Sabbaj, S., Mulligan, M. J. (2000). A Significant Number of Human Immunodeficiency Virus Epitope-Specific Cytotoxic T Lymphocytes Detected by Tetramer Binding Do Not Produce Gamma Interferon. J. Virol. 74: 10249-10255 [Abstract] [Full Text]
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Betts, M. R., Casazza, J. P., Patterson, B. A., Waldrop, S., Trigona, W., Fu, T.-M., Kern, F., Picker, L. J., Koup, R. A. (2000). Putative Immunodominant Human Immunodeficiency Virus-Specific CD8+ T-Cell Responses Cannot Be Predicted by Major Histocompatibility Complex Class I Haplotype. J. Virol. 74: 9144-9151 [Abstract] [Full Text]
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Grivel, J.-C., Malkevitch, N., Margolis, L. (2000). Human Immunodeficiency Virus Type 1 Induces Apoptosis in CD4+ but Not in CD8+ T Cells in Ex Vivo-Infected Human Lymphoid Tissue. J. Virol. 74: 8077-8084 [Abstract] [Full Text]
Cooper, L. J. N., Kalos, M., Lewinsohn, D. A., Riddell, S. R., Greenberg, P. D. (2000). Transfer of Specificity for Human Immunodeficiency Virus Type 1 into Primary Human T Lymphocytes by Introduction of T-Cell Receptor Genes. J. Virol. 74: 8207-8212 [Abstract] [Full Text]
Dela Cruz, C. S., Tan, R., Rowland-Jones, S. L., Barber, B. H. (2000). Creating HIV-1 reverse transcriptase cytotoxic T lymphocyte target structures by HLA-A2 heavy chain modifications. Int Immunol 12: 1293-1302 [Abstract] [Full Text]
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Mitsuyasu, R. T., Anton, P. A., Deeks, S. G., Scadden, D. T., Connick, E., Downs, M. T., Bakker, A., Roberts, M. R., June, C. H., Jalali, S., Lin, A. A., Pennathur-Das, R., Hege, K. M. (2000). Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4+ and CD8+ T cells in human immunodeficiency virus-infected subjects. Blood 96: 785-793 [Abstract] [Full Text]
Salerno-Gonçalves, R., Lu, W., Andrieu, J.-M. (2000). Quantitative Analysis of the Antiviral Activity of CD8+ T Cells from Human Immunodeficiency Virus-Positive Asymptomatic Patients with Different Rates of CD4+ T-Cell Decrease. J. Virol. 74: 6648-6651 [Abstract] [Full Text]
Gea-Banacloche, J. C., Migueles, S. A., Martino, L., Shupert, W. L., McNeil, A. C., Sabbaghian, M. S., Ehler, L., Prussin, C., Stevens, R., Lambert, L., Altman, J., Hallahan, C. W., de Quiros, J. C. L. B., Connors, M. (2000). Maintenance of Large Numbers of Virus-Specific CD8+ T Cells in HIV-Infected Progressors and Long-Term Nonprogressors. J. Immunol. 165: 1082-1092 [Abstract] [Full Text]
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Clark, D. R., Repping, S., Pakker, N. G., Prins, J. M., Notermans, D. W., Wit, F. W. N. M., Reiss, P., Danner, S. A., Coutinho, R. A., Lange, J. M. A., Miedema, F. (2000). T-cell progenitor function during progressive human immunodeficiency virus-1 infection and after antiretroviral therapy. Blood 96: 242-249 [Abstract] [Full Text]
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Chen, Z. W., Craiu, A., Shen, L., Kuroda, M. J., Iroku, U. C., Watkins, D. I., Voss, G., Letvin, N. L. (2000). Simian Immunodeficiency Virus Evades a Dominant Epitope-Specific Cytotoxic T Lymphocyte Response Through a Mutation Resulting in the Accelerated Dissociation of Viral Peptide and MHC Class I. J. Immunol. 164: 6474-6479 [Abstract] [Full Text]
Le Borgne, S., Février, M., Callebaut, C., Lee, S. P., Rivière, Y. (2000). CD8+-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription. J. Virol. 74: 4456-4464 [Abstract] [Full Text]
Rinaldo, C. R. Jr., Huang, X.-L., Fan, Z., Margolick, J. B., Borowski, L., Hoji, A., Kalinyak, C., McMahon, D. K., Riddler, S. A., Hildebrand, W. H., Day, R. B., Mellors, J. W. (2000). Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+ T-Lymphocyte Reactivity during Combination Antiretroviral Therapy in HIV-1-Infected Patients with Advanced Immunodeficiency. J. Virol. 74: 4127-4138 [Abstract] [Full Text]
Oxenius, A., Price, D. A., Easterbrook, P. J., O'Callaghan, C. A., Kelleher, A. D., Whelan, J. A., Sontag, G., Sewell, A. K., Phillips, R. E. (2000). Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc. Natl. Acad. Sci. USA 97: 3382-3387 [Abstract] [Full Text]
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Huang, X.-L., Fan, Z., Kalinyak, C., Mellors, J. W., Rinaldo, C. R. Jr. (2000). CD8+ T-Cell Gamma Interferon Production Specific for Human Immunodeficiency Virus Type 1 (HIV-1) in HIV-1-Infected Subjects. CVI 7: 279-287 [Abstract] [Full Text]
de Quiros, J. C. L. B., Shupert, W. L., McNeil, A. C., Gea-Banacloche, J. C., Flanigan, M., Savage, A., Martino, L., Weiskopf, E. E., Imamichi, H., Zhang, Y.-M., Adelsburger, J., Stevens, R., Murphy, P. M., Zimmerman, P. A., Hallahan, C. W., Davey, R. T. Jr., Connors, M. (2000). Resistance to Replication of Human Immunodeficiency Virus Challenge in SCID-Hu Mice Engrafted with Peripheral Blood Mononuclear Cells of Nonprogressors Is Mediated by CD8+ T Cells and Associated with a Proliferative Response to p24 Antigen. J. Virol. 74: 2023-2028 [Abstract] [Full Text]