Dendritic Cells in Transplantation and Immune-Based Therapies

Cornell University, Итак, New York, United States
Biology of Blood and Marrow Transplantation (Impact Factor: 3.4). 02/2007; 13(1 Suppl 1):23-32. DOI: 10.1016/j.bbmt.2006.10.023
Source: PubMed


Dendritic cells (DCs) are specialized, bone marrow-derived leukocytes critical to the onset of both innate and adaptive immunity. The divisions of labor among distinct human DC subtypes achieve the most effective balance between steady-state tolerance and the induction of innate and adaptive immunity against pathogens, tumors, and other insults. Maintenance of tolerance in the steady state is an active process involving resting or semimature DCs. Breakdowns in this homeostasis can result in autoimmunity. Perturbation of the steady state should first lead to the onset of innate immunity mediated by rapid responders in the form of plasmacytoid and monocyte-derived DC stimulators and natural killer (NK) and NK T-cell responders. These innate effectors then provide additional inflammatory cytokines, including interferon-gamma, which support the activation and maturation of resident and circulating populations of DCs. These are critical to the onset and expansion of adaptive immunity, including Th1, Th2, and cytotoxic T-lymphocyte responses. Rodent models are now revealing important data about distinct DC precursors, homeostasis of tissue-resident DCs, and DC turnover in response to inflammation and pathological conditions like graft-versus-host disease. The use of defined DC subtypes to stimulate both innate and adaptive immunity, either in combination or in a prime-boost vaccine sequence, may prove most useful clinically by harnessing both effector cell compartments.

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    • "Although under debate, to create the term “semi-maturation” allowed the collection of arguments for or against it and then to keep or discard it. So far, further experimental evidences for the phenotype and tolerogenic potential of semi-mature DC stages have been obtained and reviewed (Mills and McGuirk, 2004; Morelli et al., 2005; Braun et al., 2006; Nouri-Shirazi and Thomson, 2006; Rutella et al., 2006; van Duivenvoorde et al., 2006; Young et al., 2007; Frick et al., 2010; Morel and Turner, 2011). Recently, gene-expression profiling of different semi-mature DCs (TNF, Trypanosoma antigens) was compared to fully mature DCs (LPS) and revealed mainly quantitative differences between these DC types. "
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    • "cDCs and PDCs comprise two major groups of DCs in all tissues [18]. In the context of organ transplantation, cDCs are reported to be highly immunogenic and efficient in stimulation anti-T cell alloimmunity, including production of IFN-γ [19]. In contrast, pDCs have been reported to be tolerogenic [20]. "
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