Induction of Interleukin 10–Producing, Nonproliferating Cd4+ T Cells with Regulatory Properties by Repetitive Stimulation with Allogeneic Immature Human Dendritic Cells

By H. Jonuleit, E. Schmitt, Gerold Schuler, J. Knop, Alexander Enk. Journal of Experimental Medicine, 2000

1,733 citations recorded by the source corpus.

The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state. To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83− and mature CD83+ human DCs were used for stimulation of naive, allogeneic CD4+ T cells. Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells. In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by the addition of interleukin (IL)-2. Only stimulation of T cells with mature DCs resulted in an upregulation of CD154, CD69, and CD70, whereas T cells activated with immature DCs showed an early upregulation of the negative regulator cytotoxic T lymphocyte–associated molecule 4 (CTLA-4). These T cells lost their ability to produce interferon γ, IL-2, or IL-4 after several stimulations with immature DCs and differentiated into nonproliferating, IL-10–producing T cells. Furthermore, in coculture experiments these T cells inhibited the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent, but antigen-nonspecific manner. These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10–producing T cell regulatory 1–like cells by immature DCs.

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Citations in the corpus

Regulatory T cells in the control of immune pathology (2001, background): “and stimulation of T cells with immature DCs leads to the development of T cells with regulatory activit”
Tolerogenic dendritic cells and the quest for transplant tolerance (2007, background): “, and repetitive stimulation with monocyte-derived immature DCs resulted in the generation of allospecific T cells with features of T Reg cell”
Pathogen-specific T Regulatory 1 Cells Induced in the Respiratory Tract by a Bacterial Molecule that Stimulates Interleukin 10 Production by Dendritic Cells (2002, background): “It has been suggested that immature DCs may promote the expansion of IL-10–secreting or regulatory T cells (12, 40).”
Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma (2005, unknown): “Antigen-presenting cells (APCs) modulate the nature of T-cell responses, and repetitive stimulation in the presence of immature dendritic cells (DCs) has also been used to induce T-cell populations that secrete IL-10 but not pro-inflammatory cytokine”
Immunosuppressive networks in the tumour environment and their therapeutic relevance (2005, background): “, immature or partially differentiated myeloid DCs induce either suppressive T Reg cell”
CD4+CD25+ suppressor T cells: more questions than answers (2002, unknown): “Jonuleit et al.(69) repetitively stimulated naive cord-blood T cells with allogeneic iDCs and generated a population of poorly growing T cells that primarily produced IL-10.”
Regulatory T cells: friend or foe in immunity to infection? (2004, background): “Although there is some evidence that immature DCs can selectively activate regulatory T cell”
The PD-1 Pathway in Tolerance and Autoimmunity (2010, background): “It has been shown that modulating DCs to a ‘less responsive’ phenotype can increase the polarization to the Treg subset (156, 157).”
Infectious Tolerance (2002, methodology): “cells) were used for blocking experiments (14).”