CD4 regulates susceptibility to Fas ligand- and tumor necrosis factor-mediated apoptosis

被引:77
作者
Algeciras, A
Dockrell, DH
Lynch, DH
Paya, C
机构
[1] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA
[2] Mayo Clin, Div Infect Dis, Rochester, MN 55905 USA
[3] Immunex Res & Dev Corp, Dept Immunobiol, Seattle, WA 98101 USA
关键词
D O I
10.1084/jem.187.5.711
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The current knowledge of CD4 function is Limited to its role as a necessary coreceptor in TCR-initiated signaling. We have investigated whether CD4 regulates additional T cell functions. Using human primary resting CD4(+) T cells, we demonstrate that CD4 activation is sufficient to induce lymphocyte death. Immediately after CD4 cross-linking, CD4(+) T cells are rendered susceptible to apoptosis mediated by TNF or Fast. This, together with the concomitant induction of FasL within the same population, results in significant CD4(+) T cell death in vitro. The CD4-dependent induction of susceptibility to apoptosis that is mediated by TNF or Fast is protein synthesis independent but phosphorylation dependent. After CD4 activation, PKC regulates susceptibility to apoptosis mediated by Fast but not the induction of susceptibility to TNF-dependent apoptosis. Moreover, significant differences between CD3 and CD4 activation were observed with regards to the kinetics of induction of CD4(+) T cell susceptibility to Fast-and TNF-mediated apoptosis. Altogether, these results provide a model with which to study the molecular mechanisms regulating lymphocyte survival after CD4 activation, and highlight the potential role of CD4 in controlling lymphocyte apoptosis under physiological conditions or in disease states such as HIV infection.
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收藏
页码:711 / 720
页数:10
相关论文
共 53 条
  • [1] FAS LIGAND MEDIATES ACTIVATION-INDUCED CELL-DEATH IN HUMAN T-LYMPHOCYTES
    ALDERSON, MR
    TOUGH, TW
    DAVISSMITH, T
    BRADDY, S
    FALK, B
    SCHOOLEY, KA
    GOODWIN, RG
    SMITH, CA
    RAMSDELL, F
    LYNCH, DH
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (01) : 71 - 77
  • [2] REGULATION OF APOPTOSIS AND T-CELL ACTIVATION BY FAS-SPECIFIC MAB
    ALDERSON, MR
    TOUGH, TW
    BRADDY, S
    DAVISSMITH, T
    ROUX, E
    SCHOOLEY, K
    MILLER, RE
    LYNCH, DH
    [J]. INTERNATIONAL IMMUNOLOGY, 1994, 6 (11) : 1799 - 1806
  • [3] Upregulation of fas ligand expression by human immunodeficiency virus in human macrophages mediates apoptosis of uninfected T lymphocytes
    Badley, AD
    McElhinny, JA
    Leibson, PJ
    Lynch, DH
    Alderson, MR
    Paya, CV
    [J]. JOURNAL OF VIROLOGY, 1996, 70 (01) : 199 - 206
  • [4] Macrophage-dependent apoptosis of CD4(+) T lymphocytes from HIV-infected individuals is mediated by FasL and tumor necrosis factor
    Badley, AD
    Dockrell, D
    Simpson, M
    Schut, R
    Lynch, DH
    Leibson, P
    Paya, CV
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (01) : 55 - 64
  • [5] Baker SJ, 1996, ONCOGENE, V12, P1
  • [6] DISTINCT SIGNALING PROPERTIES IDENTIFY FUNCTIONALLY DIFFERENT CD4 EPITOPES
    BALDARI, CT
    MILIA, E
    DISOMMA, MM
    BALDONI, F
    VALITUTTI, S
    TELFORD, JL
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (07) : 1843 - 1850
  • [7] INTERACTIONS BETWEEN THE TYROSINE KINASES P56LCK, P59FYN AND P50CSK IN CD4 SIGNALING IN T-CELLS
    BALDARI, CT
    DISOMMA, MM
    MILIA, E
    BERGMAN, M
    TELFORD, JL
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (04) : 919 - 925
  • [8] CROSS-LINKING CD4 BY HUMAN IMMUNODEFICIENCY VIRUS-GP120 PRIMES T-CELLS FOR ACTIVATION-INDUCED APOPTOSIS
    BANDA, NK
    BERNIER, J
    KURAHARA, DK
    KURRLE, R
    HAIGWOOD, N
    SEKALY, RP
    FINKEL, TH
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (04) : 1099 - 1106
  • [9] PROTEIN KINASE-C AND T-CELL ACTIVATION
    BERRY, N
    NISHIZUKA, Y
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1990, 189 (02): : 205 - 214
  • [10] Soluble tumor necrosis factor-alpha receptor type II (sTNF alpha RII) correlates with human immunodeficiency virus (HIV) RNA copy number in HIV-infected patients
    Bilello, JA
    Stellrecht, K
    Drusano, GL
    Stein, DS
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1996, 173 (02) : 464 - 467