Differential CD4⁺ T‐cell memory responses induced by two subsets of human monocyte‐derived dendritic cells

Abstract

Summary Dendritic cells (DC) are powerful inducers of primary T‐cell responses, but their role in secondary responses has not been extensively analysed. Here, we address the role of two DC subsets derived from human CD16+ (16+ mDC) or CD16– (16– mDC) monocytes on the reactivation of memory responses. CD4+ CD45RA– memory T cells were obtained from adult blood donors, and central (TCM) and effector (TEM) memory T cells were isolated by fluorescence‐activated cell sorting with anti‐CCR7 antibodies. The 16+ mDC and 16– mDC were cocultured with autologous lymphocytes, either unpulsed or loaded with purified protein derivatives of Mycobacterium tuberculosis (PPD) or tetanus toxoid (TT), and were analysed for up to 8 days. Over a range of doses, 16+ mDC drove stronger T‐cell proliferative responses against both antigens. Overall, antigen‐specific memory cells tended to acquire a phenotype of TEM at later time‐points in the culture, whereas cells that had completed fewer cycles of division were similar to TCM. The 16+ mDC induced higher rates of proliferation on both TCM and TEM lymphocytes than 16– mDC. This phenomenon was not related to the ability of both DC to induce CD25 expression on T cells, to lower secretion of interleukin‐2, or to raise production of interleukin‐10 during T‐cell/16– mDC cocultures. The induction of TCM effector capacity in terms of interferon‐γ production was faster and more pronounced with 16+ mDC, whereas both DC had similar abilities with TEM. In conclusion, these data might reveal new potentials in vaccination protocols with 16+ mDC aimed at inducing strong responses on central memory T cells.

GM-CSF in the generation of dendritic cells from human blood monocyte precursors: Recent advances

“…Likewise, as described in the following section, CD14 bright /CD16 À monocytes were shown to differentiate into DCs endowed with distinct phenotypes and functions depending on the cytokine cocktail they were exposed to. Differential CD4 + T cell memory responses were also found to be induced by CD16 + and CD16 À monocyte subsets (Bajana et al, 2007). It remains to be elucidated whether the divergent features of DCs generated from different monocyte precursor subsets originate from a differential expression of cytokine receptors and/or from the involvement of different molecules in the signal transduction pathways triggered upon cytokine receptor engagement.…”

Improvement of dendritic-based vaccine efficacy against hepatitis B virus–related hepatocellular carcinoma by two tumor-associated antigen gene–infected dendritic cells

“…High levels of production by AFP/HBsAgDCs suggest that the cotransfected DC presents antigen through both the MHC class I and class II pathways simultaneously. Activation of CD4 ϩ T cells is significant because they play an important role in the induction and maintenance of CTL, and CD4 ϩ T cells have effector functions against MHC class II-positive tumors [37,38]. The cytokine production patterns reflect the induction of polyclonal populations of activated T cells by AFP/HBsAg-DCs, rather than the cytokine profile of an individual T cell.…”

Targeting monocyte and macrophage subpopulations for immunotherapy: a patent review (2009 – 2013)

“…To date, the source of macrophage phenotypes from independent monocyte lineages has not been clearly defined, with for example CD14 high 'inflammatory' monocytes able to differentiate to opposing anti-inflammatory M2-like macrophages upon IL-4 stimulation [5]. There is also evidence of monocyte sub-populations yielding distinct DC phenotypes [6][7][8], but DCs will not be discussed in this review.…”