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

Lookup NU author(s): Dr Amy Anderson, Bethan Sayers, Professor Muzlifah Haniffa, Dr David Swan, Julie Diboll, Dr Xiao Wang, Professor John Isaacs, Dr Catharien Hilkens

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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, 1α,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-γ/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. © Society for Leukocyte Biology.


Publication metadata

Author(s): Anderson AE, Sayers BL, Haniffa MA, Swan DJ, Diboll J, Wang XN, Isaacs JD, Hilkens CMU

Publication type: Article

Publication status: Published

Journal: Journal of Leukocyte Biology

Year: 2008

Volume: 84

Issue: 1

Pages: 124-133

Print publication date: 01/07/2008

ISSN (print): 0741-5400

ISSN (electronic):

Publisher: Society for Leukocyte Biology

URL: http://dx.doi.org/10.1189/jlb.1107744

DOI: 10.1189/jlb.1107744


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