Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Idd3 genetic interval confers protection against multiple autoimmune diseases, including type 1 diabetes and experimental autoimmune encephalomyelitis. The favored candidate gene in this interval is Il2, which is polymorphic between susceptible and resistant strains of mice. IL-2 regulates the growth/death of effector T cells as well as the generation/maintenance of regulatory T cells (Tregs), and recent studies have shown that NOD.Idd3 Tregs are more suppressive than their NOD counterparts. We have further dissected the mechanisms underlying the differential suppression by NOD and NODxIdd3 Tregs and find that it is determined by CD11b(+)CD11c(-) APCs. Thus, contrary to what might be expected, our data suggest that the differential suppressive activity of NOD and NODxIdd3 Tregs is not due to an effect of the Idd3 genetic interval on T cells but rather is due to differences in the APC compartment.
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PMID:Cutting edge: the Idd3 genetic interval determines regulatory T cell function through CD11b+CD11c- APC. 1901 31

Although many effects of staphylococcal superantigens (SAg) on T cells are well established, less is known about their effects on APC. In this study, bovine PBMC were stimulated with a low dose of staphylococcal enterotoxin C1 (SEC1). The phenotype of adherent cells (Ac) derived from bovine PBMC cultured with SEC1 [SEC1-stimulated Ac (sAc)] for 192 h was CD14(-), CD68(-), CD163(-), dendritic cell (DC)-specific ICAM-3-grabbing nonintegrin(+), MHC class II (MHC II)(high), CD11a(low), CD11b(high), CD11c(high), and CD1b(high), suggesting these cells were dendritic cells (DC). SEC1 also induced transcription of the CXCL1, -2, and -3 family, CXCL6, CCL2, and CCL5 genes in sAc, which increased rapidly but returned to basal levels by 48 h. In contrast, increased transcription of CCL3, CCL8, and CXCL12, responsible for mononuclear cell migration and chronic inflammation, was sustained. In vitro cell migration assays showed vigorous migration of granulocytes, followed by migration of mononuclear cells. The autologous MLR showed that sAc induced a dose-dependent proliferation of CD4(+) T cells and an even stronger proliferation of CD8(+) T cells. This effect was inhibited or reduced by pretreatment with mAb to CD11b, MHC II, or MHC II plus CD18. These results indicate that stimulation of bovine PBMC by SAg induces differentiation of monocytes into DC.
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PMID:Superantigen-mediated differentiation of bovine monocytes into dendritic cells. 1912 85

Trichuris muris, the mouse whipworm, is used as a laboratory model of the human parasite T. trichiura. Three laboratory isolates of T. muris exist - the E, J and S isolates. Previous data have shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates, which are expelled. The ability of the S isolate to persist is thought to be due to it secreting unique excretory/secretory antigens, which interact with APCs such that protective T cell responses do not develop. To determine whether APCs respond differently to E/S antigens from the three isolates we cultured isolate-specific E/S with bone marrow-derived macrophages (BMMPhi) and dendritic cells (BMDCs) in vitro. Markers of co-stimulation and levels of MHC-II were analysed by FACS and cytokine levels in supernatants quantified. E/S antigens from the S isolate consistently stimulated significantly higher levels of IL-10 and IL-6 from both macrophages (F4/80(+)CD11b(+)CD11c(-)) and dendritic cells (CD11c(+)CD11b(+)F4/80(-)) compared to J and E isolate E/S. If these in vitro differences in APC-derived cytokines, particularly IL-10, are biologically significant in vivo, they may contribute to the S isolate survival, by creating a regulatory cytokine environment in which protective immune responses are less effective.
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PMID:In vitro antigen presenting cell-derived IL-10 and IL-6 correlate with Trichuris muris isolate-specific survival. 1922 83

Allergic inflammation in the airway is generally considered a Th2-type immune response. However, recent studies demonstrated that Th1- and Th17-type immune responses also play important roles in this process. IFN-gamma is a Th1-type cytokine that generally counteracts the Th2 response. Although previous studies suggest that exogenous IFN-gamma suppresses allergic airway inflammation, the mechanism of suppression has not been fully clarified. In this study, we elucidated whether IFN-gamma suppresses Ag-induced immune responses including the production of Th1- and Th17-type cytokines in the lung, and examined its mechanism of action. BALB/c mice were sensitized and challenged with OVA-Ag to induce airway inflammation. An IFN-gamma-producing plasmid vector was delivered before systemic Ag sensitization. IFN-gamma suppressed indicators of Th2-type immune responses such as airway eosinophilia, IL-5 and IL-13 production in the lung, and bronchial mucus production. Moreover, IFN-gamma also suppressed the production of IL-17 and IFN-gamma itself. The suppression was not mediated by inducing regulatory T cells or by inducing apoptosis in immunocytes. Instead, IFN-gamma suppressed the Ag-presenting capacity and cytokine production of splenic dendritic cells and thus subsequently suppressed OVA-induced activation of CD4(+) T cells. Furthermore, IFN-gamma also attenuated allergic airway inflammation when delivered during the OVA challenge. Various functions of lung CD11c(+) APCs and their migration to regional lymph nodes were also suppressed. These results suggest that the Th1 cytokine IFN-gamma has broad immune regulatory potential through suppressing APC functions. They also suggest that delivery of IFN-gamma could be an effective strategy for regulating Ag-induced immune responses in the lung.
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PMID:IFN-gamma attenuates antigen-induced overall immune response in the airway as a Th1-type immune regulatory cytokine. 1954 32

The rising incidence of autoimmune diseases such as multiple sclerosis (MS) in developed countries might be due to a more hygienic environment, particularly during early life. To investigate this concept, we developed a model of neonatal exposure to a common pathogen-associated molecular pattern, LPS, and determined its impact on experimental autoimmune encephalomyelitis (EAE). Mice exposed to LPS at 2 wk of age showed a delayed onset and diminished severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE, induced at 12 wk, compared with vehicle-exposed animals. Spinal cord transcript levels of CD3epsilon and F4/80 were lower in LPS- compared with PBS-exposed EAE animals with increased IL-10 levels in the LPS-exposed group. Splenic CD11c(+) cells from LPS-exposed animals exhibited reduced MHC class II and CD83 expression but increased levels of CD80 and CD86 both before and during EAE. MOG-treated APC from LPS-exposed animals stimulated less T lymphocyte proliferation but increased expansion of CD4(+)FoxP3(+) T cells compared with APC from PBS-exposed animals. Neuropathological studies disclosed reduced myelin and axonal loss in spinal cords from LPS-exposed compared with PBS-exposed animals with EAE, and this neuroprotective effect was associated with an increased number of CD3(+)FoxP3(+) immunoreactive cells. Analyses of human brain tissue revealed that FoxP3 expression was detected in lymphocytes, albeit reduced in MS compared with non-MS patients' brains. These findings support the concept of early-life microbial exposure influencing the generation of neuroprotective regulatory T cells and may provide insights into new immunotherapeutic strategies for MS.
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PMID:Early life exposure to lipopolysaccharide suppresses experimental autoimmune encephalomyelitis by promoting tolerogenic dendritic cells and regulatory T cells. 1954 41

In allergic airway inflammation, dendritic cells (DCs) are required for Th2 generation, recruitment, and activation in the respiratory tract. DCs have been shown to be necessary and sufficient for the induction of Th1 immune responses. In Th2 immunity and allergic airway inflammation, the ability of a DC to function as the sole APC has not been tested. We show that CD11c/A(beta)(b) mice with MHC class II expression restricted to CD11c-expressing DCs develop airway neutrophilia rather than allergic airway inflammation. Although CD11c/A(beta)(b) mice are capable of Th2 recruitment and activation in the lung, Th2 priming in CD11c/A(beta)(b) mice results in IFN-gamma production. Effective Th2 generation and allergic airway inflammation was achieved in CD11c/A(beta)(b) mice after treatment with anti-IFN-gamma. These studies show that DCs alone cannot drive the development of Th2 cells but require an additional MHC class II signal to stimulate effective Th2 immunity.
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PMID:Cutting edge: Limiting MHC class II expression to dendritic cells alters the ability to develop Th2- dependent allergic airway inflammation. 1959 82

Satellite glial cells (SGC) in sensory ganglia tightly envelop the neuronal cell body to form discrete anatomical units. This type of glial cell is considered neuroectoderm-derived and provides physical support to neuron somata. There are scattered hints in the literature suggesting that SGC have an immune-related function within sensory ganglia. In this study, we addressed the hypothesis that SGC are tissue-resident APC. The immune phenotype and function of a large series (n = 40) of human trigeminal ganglia (TG) were assessed by detailed flow cytometry, in situ analyses, and functional in vitro assays. Human TG-resident SGC (TG-SGC) uniformly expressed the common leukocyte marker CD45, albeit at lower levels compared with infiltrating T cells, and the macrophage markers CD14, CD68, and CD11b. In addition, TG-SGC expressed the myeloid dendritic cell (DC) marker CD11c, the T cell costimulatory molecules CD40, CD54, CD80, and CD86 and MHC class II. However, the mature DC marker CD83 was absent on TG-SGC. Functionally, TG-SGC phagocytosed fluorescent bacteria, but were unable to induce an allogeneic MLR. Finally, TG-infiltrating T cells expressed the T cell inhibitory molecules CD94/NKG2A and PD-1, and the interacting TG-SGC expressed the cognate ligands HLA-E and PD-L1, respectively. In conclusion, the data demonstrate that human TG-SGC have a unique leukocyte phenotype, with features of both macrophages and immature myeloid DC, indicating that they have a role as TG-resident APC with potential T cell modulatory properties.
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PMID:Neuron-interacting satellite glial cells in human trigeminal ganglia have an APC phenotype. 1963 5

The mechanisms responsible for the diminished immune response seen with aging are unclear. In this study, we investigate the contributions of alterations in the lymphoid microenvironment to this decrease. Using adoptive transfer of virus-specific transgenic CD8 T cells, we demonstrate that the aged environment inhibits the clonal expansion of specific CD8 T cells from young mice during virus infection. Transferred specific CD8 T cells from young mice demonstrated a response reflecting the CD8 T cell response of the intact aged host: the CD8 T cells expand more slowly and have a decreased maximal expansion in an aged compared to a young environment. While isolated DCs (MHC II(+) CD11c(+)) of aged mice maintain their ability to support CD8 T cell Ag-specific expansion in vitro, splenocytes demonstrated an age-associated decrease in this ability. Since the percentages of various populations of DCs in splenocytes demonstrate no significant alteration with age, this diminished APC activity of splenocytes of aged mice may reflect inhibitory activity of other cell populations. The results of this study demonstrate that elements of the aged environment play an important role in the alteration of T cell response to virus infection in the aged.
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PMID:Limited expansion of virus-specific CD8 T cells in the aged environment. 1974 6

Natural killer cells are innate effector cells known for their potential to produce interferon-gamma and kill tumour and virus-infected cells. Recently, B220(+)CD11c(int)NK1.1(+) NK cells were found to also have antigen-presenting capacity like dendritic cells (DC), hence their name interferon-producing killer DC (IKDC). Shortly after discovery, it has already been questioned if IKDC really represent a separate subset of NK cells or merely represent a state of activation. Despite similarities with DCs, in vivo evidence that they behave as bona fide APCs is lacking. Here, using a model of influenza infection, we found recruitment of both conventional B220(-) NK cells and IKDCs to the lung. To study antigen-presenting capacity of NK cell subsets and compare it to cDCs, all cell subsets were sorted from lungs of infected mice and co-cultured ex vivo with antigen specific T cells. Both IKDCs and conventional NK cells as well as cDCs presented virus-encoded antigen to CD8 T cells, whereas only cDCs presented to CD4 T cells. The absence of CD4 responses was predominantly due to a deficiency in MHCII processing, as preprocessed peptide antigen was presented equally well by cDCs and IKDCs. In vivo, the depletion of NK1.1-positive NK cells and IKDCs reduced the expansion of viral nucleoprotein-specific CD8 T cells in the lung and spleen, but did finally not affect viral clearance from the lung. In conclusion, we found evidence for APC function of lung NK cells during influenza infection, but this is a feature not exclusive to the IKDC subset.
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PMID:Both conventional and interferon killer dendritic cells have antigen-presenting capacity during influenza virus infection. 1978 75

Selective gene silencing using RNA interference (RNAi) has been shown to be an efficient method for manipulation of cellular functions. In this study, we compare three previously established methods for transfection of murine bone marrow-derived DC (BM-DC). We tested the efficacy of electroporation with the Mouse Nucleofector kit((R)) from Amaxa Biosystems and lipid-based transfection methods using transfection reagents from Santa Cruz Biotechnology or Genlantis. To analyse the transfection efficacy we used FITC-conjugated siRNA as a positive control together with CD80 and CD86 specific siRNA. We show that electroporation using the Mouse Nucleofector kit((R)) from Amaxa Biosystems was not an efficient method to transfect BM-DC with siRNA in our hands. Transfection with Santa Cruz Biotechnology reagents resulted in up to 59% FITC-siRNA positive cells, but did not result in effective silencing of CD80 surface expression. In contrast, the most effective method was the lipid-based method using the siRNA transfection reagent GeneSilencer((R)) from Genlantis. This protocol resulted in up to 92% FITC-siRNA positive cells after 4 h which declined to 62% and 59% 24 and 48 h post-transfection, respectively. The transfected BM-DC remained CD11c positive, expressed high MHC class II and intermediate CD40 and were functional as APC. In conclusion, this protocol was effective for manipulation of murine BM-DC function through the use of specific siRNA and such methods can be important for the future study of DC-T cell interactions.
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PMID:A comparative study of transfection methods for RNA interference in bone marrow-derived murine dendritic cells. 1987 49


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