CD8(+) T cells play a crucial role in the control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. Recent data suggest that HIV-1-specific CD8(+) T cell subsets may differ in their ability to exert these effector functions. Here, we directly compared the cytokine secretion Patterns and cytotoxic capacity of HIV-1-specific CD8(+) T cells, using a flow-cytometric cytotoxicity assay based on caspase-3 activation in dying target cells. These experiments revealed consider- able intraindividual and interindividual differences among epitope-specific T-cell effector functions: while the frequency of HIV-1-specific CD8(+) T cells secreting interferon-gamma but no tumor necrosis factor-alpha (TNF-alpha) following antigenic stimulation was only weakly correlated to their cytotoxic activity (R = 0.05, P = .57), a subset of CD8(+) T cells secreting both interferon-gamma and TNF-a was substantially more strongly associated with cytotoxicity (R = 0.67, P < .001). This subset of CD8(+) T cells also exhibited stronger intracellular perforin expression and more pronounced direct ex vivo HIV-1-specific cytoxicity than CD8(+) T cells secreting solely interferon-gamma following sorting of these subpopulations according to their cytokine profile. These results suggest that HIV-1-specific cytotoxicity of CD8(+) T cells is preferentially mediated by a subset of CD8(+) T cells secreting both interferon-gamma and TNF-alpha. (C) 2004 by The American Society of Hematology.
机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Appay, V
Nixon, DF
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Nixon, DF
Donahoe, SM
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Donahoe, SM
Gillespie, GMA
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Gillespie, GMA
Dong, T
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Dong, T
King, A
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
King, A
Ogg, GS
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Ogg, GS
Spiegel, HML
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Spiegel, HML
Conlon, C
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Conlon, C
Spina, CA
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Spina, CA
Havlir, DV
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Havlir, DV
Richman, DD
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Richman, DD
Waters, A
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Waters, A
Easterbrook, P
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Easterbrook, P
McMichael, AJ
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John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, EnglandJohn Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
McMichael, AJ
Rowland-Jones, SL
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Appay, V
Nixon, DF
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Nixon, DF
Donahoe, SM
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Donahoe, SM
Gillespie, GMA
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Gillespie, GMA
Dong, T
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Dong, T
King, A
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
King, A
Ogg, GS
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Ogg, GS
Spiegel, HML
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Spiegel, HML
Conlon, C
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Conlon, C
Spina, CA
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Spina, CA
Havlir, DV
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Havlir, DV
Richman, DD
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Richman, DD
Waters, A
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Waters, A
Easterbrook, P
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
Easterbrook, P
McMichael, AJ
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机构:
John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, EnglandJohn Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England
McMichael, AJ
Rowland-Jones, SL
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机构:John Radcliffe Hosp, MRC, Human Immunol Unit, Inst Mol Med, Oxford OX3 9DS, England