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.
"These include many specific DC subsets that are defined both by location in the body and by specific surface markers, such as skin epidermal Langerhans cells and resident DCs present in lymphoid organs. Upon activation, cDCs produce IL-12 and promote Th1 cell differentiation and CD8 + cytotoxic T cell responses (Young et al, 2007; Koyama et al, 2009). "
[Show abstract][Hide abstract] ABSTRACT: Optimal management of complex autoimmune diseases requires a multidisciplinary medical team including dentists to care for lesions of the oral cavity. In this review, we discuss the presentation, prevalence, diagnosis, and treatment of oral manifestations in chronic graft-versus-host disease (cGVHD), which is a major late complication in patients treated by allogeneic hematopoietic stem cell transplantation. We assess current general knowledge of systemic and oral cGVHD and present general treatment recommendations based on literature review and our clinical experience. Additionally, we review areas where the understanding of oral cGVHD could be improved by further research and address tools with which to accomplish the long-term goal of providing better health and quality of life to patients with cGVHD.
"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. "
[Show abstract][Hide abstract] ABSTRACT: Dendritic cells (DCs) are major players in the control of adaptive tolerance and immunity. Therefore, their specific generation and adoptive transfer into patients or their in vivo targeting is attractive for clinical applications. While injections of mature immunogenic DCs are tested in clinical trials, tolerogenic DCs still are awaiting this step. Besides the tolerogenic potential of immature DCs, also semi-mature DCs can show tolerogenic activity but both types also bear unfavorable features. Optimal tolerogenic DCs, their molecular tool bar, and their use for specific diseases still have to be defined. Here, the usefulness of in vitro generated and adoptively transferred semi-mature DCs for tolerance induction is outlined. The in vivo targeting of semi-mature DCs as represented by steady state migratory DCs are discussed for treatment of autoimmune diseases and allergies. First clinical trials with transcutaneous allergen application may point to their therapeutic use in the future.
Frontiers in Immunology 05/2012; 3:123. DOI:10.3389/fimmu.2012.00123
"cDCs and PDCs comprise two major groups of DCs in all tissues . 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 . In contrast, pDCs have been reported to be tolerogenic . "
[Show abstract][Hide abstract] ABSTRACT: Direct allorecognition, i.e., donor lung-derived dendritic cells (DCs) stimulating recipient-derived T lymphocytes, is believed to be the key mechanism of lung allograft rejection. Myeloid (cDCs) and plasmacytoid (pDCs) are believed to have differential effects on T cell activation. However, the roles of each DC type on T cell activation and rejection pathology post lung transplantation are unknown.
Using transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2(d)) prior to transplanting into C57BL/6 mice (H-2(b)), followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+).
Depleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFNγ, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production.
Collectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.
Respiratory research 03/2012; 13(1):25. DOI:10.1186/1465-9921-13-25 · 3.09 Impact Factor
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