▪ Abstract This review summarizes the major features of CD1 genes and proteins, the patterns of intracellular trafficking of CD1 molecules, and how they sample different intracellular compartments for self- and foreign lipids. We describe how lipid antigens bind to CD1 molecules with their alkyl chains buried in hydrophobic pockets and expose their polar lipid headgroup whose fine structure is recognized by the TCR of CD1-restricted T cells. CD1-restricted T cells carry out effector, helper, and adjuvant-like functions and interact with other cell types including macrophages, dendritic cells, NK cells, T cells, and B cells, thereby contributing to both innate and adaptive immune responses. Insights gained from mice and humans now delineate the extensive range of diseases in which CD1-restricted T cells play important roles and reveal differences in the role of CD1a, CD1b, and CD1c in contrast to CD1d. Invariant TCRα chains, self-lipid reactivity, and rapid effector responses empower a subset of CD1d-restr...

CD1: antigen presentation and T cell function.

CD1 proteins present self and microbial glycolipids to CD 1-restricted T cells, or in the case of CD1d, to NKT cells. The CD1 family in humans consists of group I proteins CDla, CDlb, CDlc, and CDle and the group II protein CDld. Rodents express only CDld, but as CD1d is broadly expressed and traffics to all endosomal compartments, this single CD1 family member is thereby able to acquire antigens in many subcellular compartments. A complete understanding of the CD 1 family requires an appreciation of which cells express CD1 and how CD1 contributes to the unique function of each cell type. While group I CD 1 expression is limited to thymocytes and professional APCs, CD1d has a wider tissue distribution and can be found on many nonhematopoietic cells. The expression and regulation of CD1 are presented here with particular emphasis on the function of CD1 in thymocytes, B cells, monocytes and macrophages, dendritic cells (DCs), and intestinal epithelial cells (IECs). Altered expression of CD 1 in cancer, autoimmunity, and infectious disease is well documented, and the implication of CD 1 expression in these diseases is discussed.

CD1 Expression on Antigen-Presenting Cells

Plasmacytoid dendritic cells (pDCs) represent a DC subtype that exerts divergent functions in innate and adoptive immunity including the immediate reaction to microbial factors and the induction of immunoregulatory responses It is thought that different DC subtypes may be critically involved in the pathogenesis of multiple sclerosis (MS) In our study we assessed the phenotype, maturation and functional properties of peripheral blood pDCs from 35 clinically stable, untreated multiple sclerosis patients, 30 healthy controls and 9 patients with pneumonia, which was used as a non-specific inflammatory condition (NIC) Ex vivo expression of CD86 and 4-1BBL was significantly lower on pDCs from multiple sclerosis patients than from controls and patients with NIC (22 versus 47 versus 41% and 12 versus 35 versus 32%, respectively) When stimulated with IL-3 and CD40L, pDCs of multiple sclerosis patients showed inefficient maturation as demonstrated by significantly lower or delayed upregulation of CD86, 4-1BBL, CD40 and CD83 Additionally, in multiple sclerosis, stimulation of pDCs by unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) resulted in a significantly lower interferon (IFN) alpha secretion than in controls In multiple sclerosis, but not in controls, pDCs failed to upregulate proliferative responses and IFN-gamma secretion of autologous peripheral blood mononuclear cells (PBMC) in a co-culture system Moreover, depletion of pDCs in multiple sclerosis patients, but not in controls, had no effect on generation of CD4+Foxp3+ regulatory T cells We also provide data showing that glatiramer acetate (GA) treatment partially restores phenotype and function of pDCs in multiple sclerosis patients These findings suggest functional abnormalities of pDCs in these patients, which might be of importance in the understanding of the development of immune dysregulation in this disease

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Impaired maturation and altered regulatory function of plasmacytoid dendritic cells in multiple sclerosis.

PPARγ regulates the function of human dendritic cells primarily by altering lipid metabolism

Platelet factor 4 (PF4) is a CXC chemokine secreted by activated platelets. PF4 has been shown to promote monocyte survival and induce the differentiation of monocytes into macrophages. However, the effect of PF4 on differentiation of monocytes into dendritic cells (DC) has yet to be determined. As reported previously, monocytes cultured in RPMI medium containing FCS, granulocyte macrophage colony stimulating factor and IL-4 differentiated into CD1a+ DC. When PF4 was added, the expression of CD1a on DC was inhibited. This inhibitory effect was not observed with the other platelet-derived CXC chemokine, b-thromboglobulin. The relative number of CD1a‐ DC increased from17 to 92% when the PF4 concentration was increased from 0 to 10 mg/ml. The inhibitory effect of PF4 on CD1a expression was reversed by 50 U/ml heparin. DC developed in the PF4-containing media appeared more adhesive to plastic culture wells and had higher light side scatter by flow cytometry. Immunophenotypically, monocyte-derived DC in the presence of increasing concentrations of PF4 proportionally expressed higher CD86 and lower HLA-DR. The levels of CD11c, CD40 and CD80 remained unchanged with or without PF4. Both CD1a + DC and CD1a ‐ DC were negative for CD14, CD68 and CD83. Functionally, DC developed in the presence of PF4 had their secretion of tumor necrosis factor-a and IL-12 reduced by 75 6 10 and 79 6 13% respectively when they were stimulated by 100 ng/ml lipopolysaccharide and 50 ng/ml IFN-g. CD1a ‐ DC developed in the presence of PF4 were not as active as the control CD1a + DC in stimulating allogeneic T cells to proliferate. In addition, CD1a ‐ DC were less potent in priming naive CD4 + T cells to secrete both type 1 and 2 cytokines. These results indicate that PF4 can

Effect of CXC chemokine platelet factor 4 on differentiation and function of monocyte‐derived dendritic cells

One successful approach to generate dendritic cells (DC) is to cultivate peripheral blood monocytes in fetal calf serum (FCS)-containing medium in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4. Because the use of xenogenic proteins has to be strictly avoided for clinical applications, alternative protocols use human plasma instead of FCS. The aim of our study was to characterize DC generated in the presence of human plasma; moreover, we describe a novel protocol to generate DC directly from peripheral blood mononuclear cells (PBMC). DC generated from purified monocytes in the presence of 1% human plasma (HP-DC) and GM-CSF and IL-4 both in the allogenic mixed leukocyte reaction (MLR) and in the tetanus presentation assay were potent stimulators of T-cell proliferation. DC generated from PBMC were equally effective stimulators in the allogenic MLR as those generated from purified monocytes. When the immunophenotype of DC generated from FCS containing medium (FCS-DC) was compared to that of HP-DC, the surface expression of CD1a and CD80 was significantly lower in HP-DC. In contrast, the expression of CD83 and CD86 was significantly higher in HP-DC than in FCS-DC. The capacity of receptor mediated endocytosis and macropinocytosis was found to be significantly lower in HP-DC when compared to FCS-DC. The differences in the immunophenotype, macropinocytosis and endocytosis between the HP-DC and the FCS-DC were observed independently of the generation of the cells from PBMC or purified monocytes. Our data indicate that HP-DC are potent stimulators of T-cell proliferation and exhibit a characteristic phenotype of intermediate maturity. Moreover, DC can be directly generated from PBMC preparations.

Functional and phenotypic characteristics of dendritic cells generated in human plasma supplemented medium.

Abstract. Glacial lake outburst floods (GLOFs) are among the most
concerning consequences of retreating glaciers in mountain ranges worldwide.
GLOFs have attracted significant attention amongst scientists and
practitioners in the past 2 decades, with particular interest in the
physical drivers and mechanisms of GLOF hazard and in socioeconomic and other
human-related developments that affect vulnerabilities to GLOF events. This
increased research focus on GLOFs is reflected in the gradually increasing
number of papers published annually. This study offers an overview of recent
GLOF research by analysing 594 peer-reviewed GLOF studies published between
2017 and 2021 (Web of Science and Scopus databases), reviewing the content and
geographical focus as well as other characteristics of GLOF studies. This
review is complemented with perspectives from the first GLOF conference (7–9
July 2021, online) where a global GLOF research community of major
mountain regions gathered to discuss the current state of the art of
integrated GLOF research. Therefore, representatives from 17 countries
identified and elaborated trends and challenges and proposed possible ways
forward to navigate future GLOF research, in four thematic areas: (i) understanding GLOFs – timing and processes; (ii) modelling GLOFs and GLOF
process chains; (iii) GLOF risk management, prevention and warning; and (iv) human dimensions of GLOFs and GLOF attribution to climate change.


Knapp

Papers

Functional and phenotypic characteristics of dendritic cells generated in human plasma supplemented medium.

Progress and challenges in glacial lake outburst flood research (2017–2021): a research community perspective