Diminished proliferation of human immunodeficiency virus-specific CD4+ T cells is associated with diminished interleukin-2 (IL-2) production and is recovered by exogenous IL-2

被引:154
作者
Iyasere, C
Tilton, JC
Johnson, AJ
Younes, S
Yassine-Diab, B
Sekaly, RP
Kwok, WW
Migueles, SA
Laborico, AC
Shupert, WL
Hallahan, CW
Davey, RT
Dybul, M
Vogel, S
Metcalf, J
Connors, M
机构
[1] NIAID, LIR, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA
[2] Univ Montreal, CHUM, Immunol Lab, Montreal, PQ, Canada
[3] Benaroya Res Inst, Virginia Mason Res Ctr, Seattle, WA USA
关键词
D O I
10.1128/JVI.77.20.10900-10909.2003
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Virus-specific CD4(+) T-cell function is thought to play a central role in induction and maintenance of effective CD8(+) T-cell responses in experimental animals or humans. However, the reasons that diminished proliferation of human immunodeficiency virus (HIV)-specific CD4(+) T cells is observed in the majority of infected patients and the role of these diminished responses in the loss of control of replication during the chronic phase of HIV infection remain incompletely understood. In a cohort of 15 patients that were selected for particularly strong HIV-specific CD4(+) T-cell responses, the effects of viremia on these responses were explored. Restriction of HIV replication was not observed during one to eight interruptions of antiretroviral therapy in the majority of patients (12 of 15). In each case, proliferative responses to HIV antigens were rapidly inhibited during viremia. The frequencies of cells that produce IFN-gamma in response to Gag, Pol, and Nef peptide pools were maintained during an interruption of therapy. In a subset of patients with elevated frequencies of interleukin-2 (IL-2)-producing cells, IL-2 production in response to HIV antigens was diminished during viremia. Addition of exogenous IL-2 was sufficient to rescue in vitro proliferation of DR0101 class II Gag or Pol tetramer(+) or total-Gag-specific CD4(+) T cells. These observations suggest that, during viremia, diminished in vitro proliferation of HIV-specific CD4(+) T cells is likely related to diminished IL-2 production. These results also suggest that relatively high frequencies of HIV-specific CD4(+) T cells persist in the peripheral blood during viremia, are not replicatively senescent, and proliferate when IL-2 is provided exogenously.
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页码:10900 / 10909
页数:10
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共 55 条
  • [1] Maximum suppression of HIV replication leads to the restoration of HIV-specific responses in early HIV disease
    Al-Harthi, L
    Siegel, J
    Spritzler, J
    Pottage, J
    Agnoli, M
    Landay, A
    [J]. AIDS, 2000, 14 (07) : 761 - 770
  • [2] Frequencies of memory T cells specific for varicella-zoster virus, herpes simplex virus, and cytomegalovirus by intracellular detection of cytokine expression
    Asanuma, H
    Sharp, M
    Maecker, HT
    Maino, VC
    Arvin, AM
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2000, 181 (03) : 859 - 866
  • [3] Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses:: Relationship to viral load in untreated HIV infection
    Betts, MR
    Ambrozak, DR
    Douek, DC
    Bonhoeffer, S
    Brenchley, JM
    Casazza, JP
    Koup, RA
    Picker, LJ
    [J]. JOURNAL OF VIROLOGY, 2001, 75 (24) : 11983 - 11991
  • [4] The relationship between T cell proliferative responses and plasma viremia during treatment of human immunodeficiency virus type 1 infection with combination antiretroviral therapy
    Binley, JM
    Schiller, DS
    Ortiz, GM
    Hurley, A
    Nixon, DF
    Markowitz, MM
    Moore, JP
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2000, 181 (04) : 1249 - 1263
  • [5] Proliferative responses to human immunodeficiency virus type 1 (HIV-1) antigens in HIV-1-infected patients with immune reconstitution
    Blankson, JN
    Gallant, JE
    Siliciano, RF
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2001, 183 (04) : 657 - 661
  • [6] Therapeutic use of IL-2 to enhance antiviral T-cell responses in vivo
    Blattman, JN
    Grayson, JM
    Wherry, EJ
    Kaech, SM
    Smith, KA
    Ahmed, R
    [J]. NATURE MEDICINE, 2003, 9 (05) : 540 - 547
  • [7] Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B
    Boni, C
    Bertoletti, A
    Penna, A
    Cavalli, A
    Pilli, M
    Urbani, S
    Scognamiglio, P
    Boehme, R
    Panebianco, R
    Fiaccadori, F
    Ferrari, C
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (05) : 968 - 975
  • [8] Progressive loss of CD8(+) T cell-mediated control of a gamma-herpesvirus in the absence of CD4(+) T cells
    Cardin, RD
    Brooks, JW
    Sarawar, SR
    Doherty, PC
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (03) : 863 - 871
  • [9] MECHANISMS OF IMMUNOSUPPRESSION IN CYTOMEGALO-VIRUS MONONUCLEOSIS .2. VIRUS-MONOCYTE INTERACTIONS
    CARNEY, WP
    HIRSCH, MS
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1981, 144 (01) : 47 - 54
  • [10] Detection of antigen-specific T cells with multivalent soluble class II MHC covalent peptide complexes
    Crawford, F
    Kozono, H
    White, J
    Marrack, P
    Kappler, J
    [J]. IMMUNITY, 1998, 8 (06) : 675 - 682