Premium
Differential regulation of naïve and memory CD4 + T cells by alternatively activated dendritic cells
Author(s) -
Anderson Amy E.,
Sayers Bethan L.,
Haniffa Muzlifah A.,
Swan David J.,
Diboll Julie,
Wang Xiaog,
Isaacs John D.,
Hilkens Catharien M. U.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1107744
Subject(s) - biology , priming (agriculture) , cytotoxic t cell , t cell , microbiology and biotechnology , interleukin 3 , cytokine , immunology , cd28 , cd8 , interleukin 21 , immune system , in vitro , biochemistry , botany , germination
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 CD25 hi 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.