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Differential regulation of naïve and memory CD4+ T cells by alternatively activated dendritic cells.

Anderson, Amy E, Sayers, Bethan L, Haniffa, Muzlifah A, Swan, David, Diboll, Julie, Wang, Xiao-Nong, Isaacs, John D and Hilkens, Catharien M U (2008) Differential regulation of naïve and memory CD4+ T cells by alternatively activated dendritic cells. Journal of leukocyte biology, 84 (1). pp. 124-133. ISSN 0741-5400

Item Type: Article

Abstract

Promising immunotherapeutic tools for T cell-mediated pathologies are alternatively activated dendritic cells (aaDC), which exert their effect through the regulation and tolerization of T cells. As naïve and memory T cells have different susceptibilities to tolerogenic signals, it is important to understand the modulatory effects of aaDC on these T cell subsets. We have examined regulation of naïve and memory CD4+ T cells by human aaDC generated with dexamethasone, the active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3, and LPS. Although aaDC induced low, primary, allogeneic responses by naïve and memory T cells, aaDC regulated the differentiation of these T cell subsets in a distinct manner. Naïve T cells primed by aaDC retained a strong, proliferative capacity upon restimulation but were skewed toward a low IFN-gamma/high IL-10 cytokine profile. In contrast, memory T cells primed by aaDC became hyporesponsive in terms of proliferation and cytokine production. Induction of anergy in memory T cells by aaDC was not a result of the presence of CD25hi regulatory T cells and could be partially reversed by IL-2. Both T cell subsets acquired regulatory activity and inhibited primary CD4 and CD8 responses. Addition of exogenous IL-12p70 during T cell priming by aaDC prevented anergy induction in memory T cells and cytokine polarization in naïve T cells, indicating that the lack of IL-12p70 is a key feature of aaDC. Our finding that aaDC differentially regulate naïve and memory T cells is important for understanding and maximizing the therapeutic potential of aaDC.

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More Information

Uncontrolled Keywords: tolerance, cytokine deviation, hyporesponsiveness, immunotherapy
Depositing User: David Swan

Identifiers

Item ID: 16677
Identification Number: https://doi.org/10.1189/jlb.1107744
ISSN: 0741-5400
URI: http://sure.sunderland.ac.uk/id/eprint/16677
Official URL: https://academic.oup.com/jleukbio/article/84/1/124...

Users with ORCIDS

ORCID for David Swan: ORCID iD orcid.org/0000-0002-6480-9621

Catalogue record

Date Deposited: 03 Oct 2023 14:44
Last Modified: 24 Apr 2024 12:48

Contributors

Author: David Swan ORCID iD
Author: Amy E Anderson
Author: Bethan L Sayers
Author: Muzlifah A Haniffa
Author: Julie Diboll
Author: Xiao-Nong Wang
Author: John D Isaacs
Author: Catharien M U Hilkens

Subjects

Sciences > Biomedical Sciences

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