Title:
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Neonatal tumor necrosis factor alpha promotes diabetes in nonobese diabetic mice by CD154-independent antigen presentation to CD8(+) T cells
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Author:
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Green, E. Allison; Wong, F. Susan; Eshima, Koji; Mora Giral, Concepció; Flavell, Richard A.
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Notes:
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Neonatal islet-specific expression of tumor necrosis factor (TNF)-α 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-α 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-α–mediated diabetes development was not dependent on CD154–CD40 signals or activated CD4+ T cells. Instead, it appears that TNF-α 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 can bypass CD154–CD40 immune regulatory signals and cause activation of autoreactive T cells. |
Subject(s):
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-CD154 -Diabetes -NOD mice -CD8+ cells |
Rights:
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cc-by-nc-sa, (c) Green et al., 2000
http://creativecommons.org/licenses/by-nc-sa/3.0/es/
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Document type:
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article publishedVersion |
Published by:
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Rockefeller University Press
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