Antigen-Specific Inhibition of Effector T Cell Function in Humans after Injection of Immature Dendritic Cells

By M. Dhodapkar, R. Steinman, J. Krasovsky, C. Munz, N. Bhardwaj. Journal of Experimental Medicine, 2001

1,511 citations recorded by the source corpus.

Immunostimulatory properties of dendritic cells (DCs) are linked to their maturation state. Injection of mature DCs rapidly enhances antigen-specific CD4+ and CD8+ T cell immunity in humans. Here we describe the immune response to a single injection of immature DCs pulsed with influenza matrix peptide (MP) and keyhole limpet hemocyanin (KLH) in two healthy subjects. In contrast to prior findings using mature DCs, injection of immature DCs in both subjects led to the specific inhibition of MP-specific CD8+ T cell effector function in freshly isolated T cells and the appearance of MP-specific interleukin 10–producing cells. When pre- and postimmunization T cells were boosted in culture, there were greater numbers of MP-specific major histocompatibility complex tetramer-binding cells after immunization, but these had reduced interferon γ production and lacked killer activity. These data demonstrate the feasibility of antigen-specific inhibition of effector T cell function in vivo in humans and urge caution with the use of immature DCs when trying to enhance tumor or microbial immunity.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/bf3c8ffa1e662bb9c7510075f9ab9e258fe2dffe

How researchers see this paper

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In Immunology

1. Jacques Banchereau
2. Yong‐jun Liu
3. A. O’Garra
4. W. Zou
5. R. Steinman
6. F. Powrie
7. E. Shevach
8. A. Thomson

Citations in the corpus

• Human Dendritic Cells Activate Resting Natural Killer (NK) Cells and Are Recognized via the NKp30 Receptor by Activated NK Cells (2002, background): “Another possible outcome relates to recent information that immature DCs may induce IL-10–producing regulatory T cells (57, 58).”
• Regulatory T Cells Induced by 1α,25-Dihydroxyvitamin D3 and Mycophenolate Mofetil Treatment Mediate Transplantation Tolerance1 (2001, background): “Mechanistically, immature DCs could favor peripheral tolerance not only by decreasing the activation of effector T cells but also by inducing the differentiation of T regulatory cells (50, 51).”
• Regulation of T cell immunity by dendritic cells. (2001, background): “In IL-10 and IFN- (Cella et al., 2000; Kadowaki et al., 2000).”
• CD4+CD25+ suppressor T cells: more questions than answers (2002, positive): “Immature DCs are the ideal population to prime regulatory T cells as they are deficient in co-stimulatory molecules, and priming with antigen–iDC complexes might even be able to downregulate pre-existing antigen-specific immune response”
• 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”
• Immunosuppressive networks in the tumour environment and their therapeutic relevance (2005, background): “, immature or partially differentiated myeloid DCs induce either suppressive T Reg cell”
• Antigen-presenting cell function in the tolerogenic liver environment (2010, background): “and/or downregulators of TLR signalling or by the adoptive transfer of ex vivo -expanded and peptide-loaded liver DCs (as shown for model antigen”
• 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).”
• Generation of Human CD8 T Regulatory Cells by CD40 Ligand–activated Plasmacytoid Dendritic Cells (2002, background): “A recent study described IL-10–producing CD8 T cells in vivo in concomitance with a decreased influenza-specific CD8 T cell response after vaccination with immature DC1 pulsed with influenza matrix peptide (36).”
• The enemy within: keeping self-reactive T cells at bay in the periphery (2002, positive): “Efforts to unravel the defining characteristics of a tolerogenic versus a stimulatory DC have led to pioneering studies in humans using antigen-pulsed immature DCs to successfully induce T-cell toleranc”
• Dendritic cells as therapeutic vaccines against cancer (2005, background): “or to the development of IL-10-secreting INDUCIBLE REGULATORY T CELLS”