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IL-2 is required for the activation of memory CD8+ T cells via antigen cross-presentation.

Résumé : Dendritic cells (DCs) are capable of capturing exogenous Ag for the generation of MHC class I/peptide complexes. For efficient activation of memory CD8(+) T cells to occur via a cross-presentation pathway, DCs must receive helper signals from CD4(+) T cells. Using an in vitro system that reflects physiologic recall memory responses, we have evaluated signals that influence helper-dependent cross-priming, while focusing on the source and cellular target of such effector molecules. Concerning the interaction between CD4(+) T cells and DCs, we tested the hypothesis that CD40 engagement on DCs is critical for IL-12p70 (IL-12) production and subsequent stimulation of IFN-gamma release by CD8(+) T cells. Although CD40 engagement on DCs, or addition of exogenous IL-12 are both sufficient to overcome the lack of help, neither is essential. We next evaluated cytokines and chemokines produced during CD4(+) T cell/DC cross talk and observed high levels of IL-2 produced within the first 18-24 h of Ag-specific T cell engagement. Functional studies using blocking Abs to CD25 completely abrogated IFN-gamma production by the CD8(+) T cells. Although required, addition of exogenous IL-2 did not itself confer signals sufficient to overcome the lack of CD4(+) T cell help. Thus, these data support a combined role for Ag-specific, cognate interactions at the CD4(+) T cell/DC as well as the DC/CD8(+) T cell interface, with the helper effect mediated by soluble noncognate signals.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01402330
Contributor : Marie-Christine Vougny <>
Submitted on : Thursday, November 24, 2016 - 3:24:16 PM
Last modification on : Friday, April 3, 2020 - 9:42:51 AM

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Nathalie E Blachère, Heather K Morris, Deborah Braun, Hélène Saklani, James P Di Santo, et al.. IL-2 is required for the activation of memory CD8+ T cells via antigen cross-presentation.. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2006, 176 (12), pp.7288-300. ⟨10.4049/jimmunol.176.12.7288⟩. ⟨pasteur-01402330⟩

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