Journal of Leukocyte Biology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published online as doi:10.1189/jlb.1107744 on April 22, 2008

Published online before print April 22, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.1107744v1
84/1/124    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Anderson, A. E.
Right arrow Articles by Hilkens, C. M. U.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Anderson, A. E.
Right arrow Articles by Hilkens, C. M. U.
(Journal of Leukocyte Biology. 2008;84:124-133.)
© 2008 by Society for Leukocyte Biology

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

Amy E. Anderson*,1, Bethan L. Sayers*,1, Muzlifah A. Haniffa*,{dagger},{ddagger}, David J. Swan*, Julie Diboll*, Xiao-Nong Wang{dagger}, John D. Isaacs* and Catharien M. U. Hilkens*,2

* Musculoskeletal Research Group,
{dagger} Hematological Sciences, and
{ddagger} Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

2Correspondence: Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor Catherine Cookson Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. E-mail: catharien.hilkens{at}newcastle.ac.uk

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, 1{alpha},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.

Key Words: tolerance • cytokine deviation • hyporesponsiveness • immunotherapy







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Society for Leukocyte Biology.