Identification of progenitor cells in long-term spleen stromal cultures that produce immature dendritic cells

Wilson, Heather L.; Ni, Keping; O’Neill, Helen C.

doi:10.1073/pnas.080278897

Cited by 64 publications

(104 citation statements)

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“…As anticipated, all dendritic cells expressed CD80, but only a few were seen to express CD40 or CD86. It has been demonstrated elsewhere (27) that this phenotype tends to identify large immature cells. Lung dendritic cells infected with M. tuberculosis and cultured overnight exhibited little change in the expression of CD40, CD80, CD86, and I-A antigens.…”

Section: Discussionmentioning

confidence: 99%

“…Compared to the total numbers of cells that could be harvested from the lungs, their numbers were low. Following flow cytometric analysis it was found that the great majority of these dendritic cells had a marker expression that is generally regarded by most studies (21,27) as an immature phenotype, i.e., CD11c mid to high and major histocompatibility (MHC) class II low . A small number of cells, however, expressed high levels of I-A (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of Murine Lung Dendritic Cells Infected withMycobacterium tuberculosis

2001

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Lung dendritic cells were identified by immunohistochemistry in lung tissue sections from C57BL/6 mice. Following isolation from the lungs using CD11c magnetic beads, the flow cytometric analysis of I-A b؉ and CD11c؉ cells indicated a mixed population of dendritic cells at different stages of maturation, with most expressing an immature phenotype. When cultured for 7 days with recombinant murine granulocyte-macrophage colony-stimulating factor, 99% of cells were CD11c ؉ and had a morphology typical of immature dendritic cells. These cells were negative for CD34, CD14, and CD8␣ antigens but expressed low levels of the myeloid marker F4/80 and moderate levels of MAC3. All expressed high levels of CD11a (LFA-1), CD11b (Mac1), and CD54 antigens, with low levels of class II major histocompatibility complex. Most cells expressed CD80 but only a small percentage of cells were positive for CD40 and CD86. Both overnight and 7-day cultures of lung dendritic cells were able to phagocytose Mycobacterium tuberculosis, and this was associated with the production of interleukin-12 and stimulation of both naïve and immune T cells to produce gamma interferon.Disease caused by Mycobacterium tuberculosis continues to be the major cause of mortality from infectious disease worldwide (2). While development of new chemotherapy as well as effective administration of current therapies may provide some reduction in the incidence of tuberculosis in the near term, in the longer term an effective vaccine against the disease would be preferred. However, while current innovation in new vaccine development is encouraging (16,18,19), the field is still limited by a lack of precise knowledge of the host response, especially that regarding early events soon after exposure to the bacillus.It is generally believed that the first cell to encounter M. tuberculosis in the lungs is the alveolar macrophage. If the macrophage is unable to kill the bacillus, it is thought that M. tuberculosis then somehow erodes into the interstitium, where it encounters other macrophages (how this happens is more a case of speculation [17] than of hard evidence) and thus establishes a site of infection. An influx of macrophages, probably of both local and blood-borne origin, then ensues, thickening the septa and giving rise to a local interstitial pneumonitis.Acquired immunity is expressed relatively slowly in the lungs (5, 7). The reason for this is unclear, as is the site where the protective T cells become sensitized. The lymphoid tissues surrounding the bronchi are potential sites, but for these to be the sites, antigen has to be physically carried to these tissues due to the lack of lymphatic drainage to the mouse alveolus.One type of myeloid cell capable of such an action is the dendritic cell. In the current study it is shown that CD11c-positive dendritic cells are well distributed throughout the alveolar region, with most exhibiting an immature phenotype when isolated and analyzed by flow cytometry. The study demonstrates that these cells are capable of phagocyt...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of Murine Lung Dendritic Cells Infected withMycobacterium tuberculosis

2001

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“…In addition to the induction of Treg cell expansion or generation, regulatory DC may also regulate directly the fate of effector CD4 T cells via other manners such as induction of T cell anergy, which is being widely investigated. It has been shown that splenic stromal cells can regulate DC differentiation and function (21,24,25). Our previous data showed that splenic stroma could drive mDC or hematopoietic stem cells to differentiate into regulatory DC subset, designated as differentiated DC (diffDC), which strongly inhibited T cell response via NO production (17,18), indicating the important role of splenic microenvironment in the negative control of T cell response.…”

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confidence: 99%

Splenic Stroma-Educated Regulatory Dendritic Cells Induce Apoptosis of Activated CD4 T Cells via Fas Ligand-Enhanced IFN-γ and Nitric Oxide

Guo

et al. 2012

The Journal of Immunology

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Stromal microenvironments of bone marrow, lymph nodes, and spleen have been shown to be able to regulate immune cell differentiation and function. Our previous studies demonstrate that splenic stroma could drive mature dendritic cells (DC) to further proliferate and differentiate into regulatory DC subset that could inhibit T cell response via NO. However, how splenic stroma-educated regulatory DC release NO and whether other molecules are involved in the suppression of T cell response remain unclear. In this study, we show that splenic stroma educates regulatory DC to express high level of Fas ligand (FasL) by TGF-β via ERK activation. The findings, that inhibition of CD4 T cell proliferation by regulatory DC required cell-to-cell contact and FasL deficiency impaired inhibitory effect of regulatory DC, indicate that regulatory DC inhibit CD4 T cell proliferation via FasL. Then, regulatory DC have been found to be able to induce apoptosis of activated CD4 T cells via FasL in caspase 8- and caspase 3-dependent manner. Interestingly, FasL on regulatory DC enhanced IFN-γ production from activated CD4 T cells, and in turn T cell-derived IFN-γ induced NO production from regulatory DC, working jointly to induce apoptosis of activated CD4 T cells. Blockade of IFN-γ and NO could reduce the apoptosis induction. Therefore, our results demonstrated that splenic stroma-educated regulatory DC induced T cell apoptosis via FasL-enhanced T cell IFN-γ and DC NO production, thus outlining a new way for negative regulation of T cell responses and maintenance of immune homeostasis by regulatory DC and splenic stromal microenvironment.

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“…29 It was reported that a unique subset of progenitor cells could differentiate into immature DCs after long-term culture, with a CD11c low CD11b high MHCII low CD86 low DC phenotype. 30 Subsequent research examined the influence of lymphoid microenvironments on DCs and found that both contact with stromal cells and TGF-b promoted mature DCs, with a CD11c high CD11b low MHCII high DC phenotype, to differentiate into a regulatory DC subset, with a CD11c low CD11b high -MHCII low CD86 low DC phenotype. 31 Splenic stromal cells, which mimic the secondary lymph organ microenvironment, can drive mDCs to proliferate and differentiate into a novel DCreg subset that is CD11b high Ia low and produces increased amounts of IL-10 but minimal IL-12p70, which inhibits T-cell proliferation.…”

Section: The Induction Of Tol-dcsmentioning

confidence: 99%

Tolerogenic dendritic cells and their applications in transplantation

Shi

2014

Cell Mol Immunol

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In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells (tol-DCs) with immunoregulatory functions have attracted much attention as they play important roles in inducing and maintaining immune tolerance. Here, we focused on tol-DCs that have the potential to promote immune tolerance after solid-organ transplantation. We focus on their development and interactions with other regulatory cells, and we also explore various tol-DC engineering protocols. Harnessing tol-DCs represents a promising cellular therapy for promoting long-term graft functional survival in transplant recipients that will most likely be achieved in the future.

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Identification of progenitor cells in long-term spleen stromal cultures that produce immature dendritic cells

Cited by 64 publications

References 28 publications

Characterization of Murine Lung Dendritic Cells Infected withMycobacterium tuberculosis

Characterization of Murine Lung Dendritic Cells Infected withMycobacterium tuberculosis

Splenic Stroma-Educated Regulatory Dendritic Cells Induce Apoptosis of Activated CD4 T Cells via Fas Ligand-Enhanced IFN-γ and Nitric Oxide

Tolerogenic dendritic cells and their applications in transplantation

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