Definition of leukocyte subsets in primate central nervous system by polychromatic flow cytometry

Bischoff, Tanja; Stahl–Hennig∥, Christiane; Mätz‐Rensing, Kerstin; Koutsilieri, Eleni; Sopper, Sieghart

doi:10.1002/cyto.a.21046

Cited by 5 publications

(5 citation statements)

References 57 publications

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“…Specifically, we prepared Figure 1C). These results are consistent with those obtained from humans, nonhuman primates (NHPs), and WT mice and demonstrate that, in the absence of inflammation or any other stimulus, immune cells are present in the brain under normal conditions (46)(47)(48)(49)(50)(51).…”

Section: Resultssupporting

confidence: 89%

T cells establish and maintain CNS viral infection in HIV-infected humanized mice

Honeycutt

Liao

Nixon

et al. 2018

Journal of Clinical Investigation

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The human brain is an important site of HIV replication and persistence during antiretroviral therapy (ART). Direct evaluation of HIV infection in the brains of otherwise healthy individuals is not feasible; therefore, we performed a large-scale study of bone marrow/liver/thymus (BLT) humanized mice as an in vivo model to study HIV infection in the brain. Human immune cells, including CD4+ T cells and macrophages, were present throughout the BLT mouse brain. HIV DNA, HIV RNA, and/or p24+ cells were observed in the brains of HIV-infected animals, regardless of the HIV isolate used. HIV infection resulted in decreased numbers of CD4+ T cells, increased numbers of CD8+ T cells, and a decreased CD4+/CD8+ T cell ratio in the brain. Using humanized T cell-only mice (ToM), we demonstrated that T cells establish and maintain HIV infection of the brain in the complete absence of human myeloid cells. HIV infection of ToM resulted in CD4+ T cell depletion and a reduced CD4+/CD8+ T cell ratio. ART significantly reduced HIV levels in the BLT mouse brain, and the immune cell populations present were indistinguishable from those of uninfected controls, which demonstrated the effectiveness of ART in controlling HIV replication in the CNS and returning cellular homeostasis to a pre-HIV state.

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Section: Resultssupporting

confidence: 89%

T cells establish and maintain CNS viral infection in HIV-infected humanized mice

Honeycutt

Liao

Nixon

et al. 2018

Journal of Clinical Investigation

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“…To determine the PDPN + myeloid cell type in gliomas we combined the CD11b and PDPN staining with CD45. Our analysis indicated that Pdpn is primarily expressed by CD11b + CD45 high SSC high cells (Figures 1C,D), a population that has previously been described as infiltrating macrophages (43–45). This is in line with in vitro experiments, where we cultivated murine microglia, bone marrow-derived macrophages (BMDM) and spleen macrophages in the absence and presence of LN308 glioma cells (Figure 1E).…”

Section: Resultssupporting

confidence: 62%

Podoplanin Positive Myeloid Cells Promote Glioma Development by Immune Suppression

et al. 2019

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The dynamic and interactive tumor microenvironment is conceived as a considerable parameter in tumor development and therapy response. Implementing this knowledge in the development of future cancer treatments could provide novel options in the combat of highly aggressive and difficult-to-treat tumors such as gliomas. One compartment of the tumor microenvironment that has gained growing interest is the immune system. As endogenous defense machinery the immune system has the capacity to fight against cancer cells. This, however, is frequently circumvented by tumor cells engaging immune-regulatory mechanisms that disable tumor-directed immune responses. Thus, in order to unlock the immune system against cancer cells, it is crucial to characterize in great detail individual tumor-associated immune cell subpopulations and dissect whether and how they influence immune evasion. In this study we investigated the function of a tumor-associated myeloid cell subpopulation characterized by podoplanin expression on the development of high-grade glioma tumors. Here, we show that the deletion of podoplanin in myeloid cells results in increased (CD8 + ) T-cell infiltrates and significantly prolonged survival in an orthotopic transplantation model. In vitro co-cultivation experiments indicate a podoplanin-dependent transcriptional regulation of arginase-1, a well-known player in myeloid cell-mediated immune suppression. These findings identify podoplanin positive myeloid cells as one novel mediator of the glioma-induced immune suppression. Thus, the targeted ablation of podoplanin positive myeloid cells could be included in combinatorial cancer therapies to enhance immune-mediated tumor elimination.

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“…FCM technique can be applied to detecting expression of multiple target molecules in a large numbers of brain cells simultaneously, such as exemplified in ref. . However, utilization of this technique is limited to analysis of cells grown in culture and not applicable to tissues or cell populations, which need to be analysed as a network.…”

Section: Discussionmentioning

confidence: 99%

Cytometry in the brain: studying differentiation to diagnostic applications in brain disease and regeneration therapy

et al. 2014

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During brain development, a population of uniform embryonic cells migrates and differentiates into a large number of neural phenotypes - origin of the enormous complexity of the adult nervous system. Processes of cell proliferation, differentiation and programmed death of no longer required cells, do not occur only during embryogenesis, but are also maintained during adulthood and are affected in neurodegenerative and neuropsychiatric disease states. As neurogenesis is an endogenous response to brain injury, visible as proliferation (of to this moment silent stem or progenitor cells), its further stimulation can present a treatment strategy in addition to stem cell transfer for cell regeneration therapy. Concise techniques for studying such events in vitro and in vivo permit understanding of underlying mechanisms. Detection of subtle physiological alterations in brain cell proliferation and neurogenesis can be explored, that occur during environmental stimulation, exercise and ageing. Here, we have collected achievements in the field of basic research on applications of cytometry, including automated imaging for quantification of morphological or fluorescence-based parameters in cell cultures, towards imaging of three-dimensional brain architecture together with DNA content and proliferation data. Multi-parameter and more recently in vivo flow cytometry procedures, have been developed for quantification of phenotypic diversity and cell processes that occur during brain development as well as in adulthood, with importance for therapeutic approaches.

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Definition of leukocyte subsets in primate central nervous system by polychromatic flow cytometry

Cited by 5 publications

References 57 publications

T cells establish and maintain CNS viral infection in HIV-infected humanized mice

T cells establish and maintain CNS viral infection in HIV-infected humanized mice

Podoplanin Positive Myeloid Cells Promote Glioma Development by Immune Suppression

Cytometry in the brain: studying differentiation to diagnostic applications in brain disease and regeneration therapy

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