Direct measurement of CD4+ and CD8+ T-cell responses to CMV in HIV-1-infected subjects

被引:83
作者
Komanduri, KV
Donahoe, SM
Moretto, WJ
Schmidt, DK
Gillespie, G
Ogg, GS
Roederer, M
Nixon, NF
McCune, JM
机构
[1] Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
[2] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
[3] Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
[4] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA
[5] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[6] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
关键词
AIDS; HIV; infectious immunity virus; T lymphocytes; human; FACS;
D O I
10.1006/viro.2000.0697
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Data from murine models of chronic viral infection suggest that CD4+ T-cell responses to viral pathogens are important in sustaining the number and/or function of CD8+ cytotoxic T-cell (CTL) effecters. In this study, we used cytokine flow cytometry (CFC), staining with HLA-A*0201-peptide tetramers, and peptide stimulation with epitopic peptides to study functional CD4+ and CD8+ T-cell responses to cytomegalovirus (CMV) in human subjects coinfected with CMV and the human immunodeficiency virus, type 1 (HIV-1). We show that strong CD4+ and CD8+ T-cell responses to CMV antigens are sustained over time in HIV-1-infected individuals. Those who maintain a strong CD4+ T-cell response to CMV are also likely to maintain higher frequencies of CD8+ T cells capable of binding to HLA-A*0201-CMV pp65 (A2-pp65) tetramers as well as responses to pp65 peptide stimulation with effector cytokine production. These data support the hypothesis that declines in frequencies of CD4+ T-cell responses to CMV are associated with an inability to sustain high levels of CMV-specific CD8+ T-cell responses in HIV-1-infected subjects. These declines may precede the onset of CMV-associated end organ disease. (C) 2001 Academic Press.
引用
收藏
页码:459 / 470
页数:12
相关论文
共 32 条
  • [11] The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses
    Kalams, SA
    Walker, BD
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (12) : 2199 - 2204
  • [12] T-cell epitope mapping by flow cytometry
    Kern, F
    Surel, IP
    Brock, C
    Freistedt, B
    Radtke, H
    Scheffold, A
    Blasczyk, R
    Reinke, P
    Schneider-Mergener, J
    Radbruch, A
    Walden, P
    Volk, HD
    [J]. NATURE MEDICINE, 1998, 4 (08) : 975 - 978
  • [13] Restoration of cytomegalovirus-specific CD4+ T-lymphocyte responses after ganciclovir and highly active antiretroviral therapy in individuals infected with HIV-1
    Komanduri, KV
    Viswanathan, MN
    Wieder, ED
    Schmidt, DK
    Bredt, BM
    Jacobson, MA
    McCune, JM
    [J]. NATURE MEDICINE, 1998, 4 (08) : 953 - 956
  • [14] Ljungman P, 1998, BONE MARROW TRANSPL, V21, pS72
  • [15] CD4(+) T-CELLS ARE REQUIRED TO SUSTAIN CD8(+) CYTOTOXIC T-CELL RESPONSES DURING CHRONIC VIRAL-INFECTION
    MATLOUBIAN, M
    CONCEPCION, RJ
    AHMED, R
    [J]. JOURNAL OF VIROLOGY, 1994, 68 (12) : 8056 - 8063
  • [16] Tracking antigen-specific helper T cell responses
    McHeyzerWilliams, MG
    Altman, JD
    Davis, MM
    [J]. CURRENT OPINION IN IMMUNOLOGY, 1996, 8 (02) : 278 - 284
  • [17] IDENTIFICATION OF THE MAJOR LATE HUMAN CYTOMEGALOVIRUS MATRIX PROTEIN PP65 AS A TARGET ANTIGEN FOR CD8(+) VIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTES
    MCLAUGHLINTAYLOR, E
    PANDE, H
    FORMAN, SJ
    TANAMACHI, B
    LI, CR
    ZAIA, JA
    GREENBERG, PD
    RIDDELL, SR
    [J]. JOURNAL OF MEDICAL VIROLOGY, 1994, 43 (01) : 103 - 110
  • [18] Counting antigen-specific CD8 T cells: A reevaluation of bystander activation during viral infection
    Murali-Krishna, K
    Altman, JD
    Suresh, M
    Sourdive, DJD
    Zajac, AJ
    Miller, JD
    Slansky, J
    Ahmed, R
    [J]. IMMUNITY, 1998, 8 (02) : 177 - 187
  • [19] HLA-peptide tetrameric complexes
    Ogg, GS
    McMichael, AJ
    [J]. CURRENT OPINION IN IMMUNOLOGY, 1998, 10 (04) : 393 - 396
  • [20] Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA
    Ogg, GS
    Jin, X
    Bonhoeffer, S
    Dunbar, PR
    Nowak, MA
    Monard, S
    Segal, JP
    Cao, YZ
    Rowland-Jones, SL
    Cerundolo, V
    Hurley, A
    Markowitz, M
    Ho, DD
    Nixon, DF
    McMichael, AJ
    [J]. SCIENCE, 1998, 279 (5359) : 2103 - 2106