Neonatal islet-specific expression of tumor necrosis factor (TNF)-alpha in nonobese diabetic mice promotes diabetes by provoking islet-infiltrating antigen-presenting cells to present islet peptides to autoreactive T cells. Here we show that TNF-alpha promotes autoaggression of both effector CD4(+) and CD8(+) T cells. Whereas CD8(+) T cells are critical for diabetes progression, CD4(+) T cells play a lesser role. TNF-alpha-mediated diabetes development was not dependent on CD154-CD40 signals or activated CD4(+) T cells. Instead, it appears that TNF-alpha can promote cross-presentation of islet antigen to CD8(+) T cells using a unique CD40-CD154-independent pathway. These data provide new insights into the mechanisms by which inflammatory stimuli call bypass CD151-CD40 immune regulatory signals and cause activation of autoreactive T cells.
机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Bennett, SRM
;
Carbone, FR
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PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, AustraliaPO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Carbone, FR
;
Karamalis, F
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机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Karamalis, F
;
Flavell, RA
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机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Flavell, RA
;
Miller, JFAP
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机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Miller, JFAP
;
Heath, WR
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机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Bennett, SRM
;
Carbone, FR
论文数: 0引用数: 0
h-index: 0
机构:
PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, AustraliaPO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Carbone, FR
;
Karamalis, F
论文数: 0引用数: 0
h-index: 0
机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Karamalis, F
;
Flavell, RA
论文数: 0引用数: 0
h-index: 0
机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Flavell, RA
;
Miller, JFAP
论文数: 0引用数: 0
h-index: 0
机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia
Miller, JFAP
;
Heath, WR
论文数: 0引用数: 0
h-index: 0
机构:PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Melbourne, Vic 3050, Australia