132 research outputs found

    Signaling for NKT cell development: the SAP–FynT connection

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    New studies demonstrate a critical role for the adaptor protein SAP (SLAM-associated protein) during NKT cell development. By connecting homotypic SLAM family receptor interactions with the FynT Src kinase, SAP may integrate a set of long-standing yet seemingly disparate observations characterizing NKT cell development. In fact, SAP-dependent signaling may underlie the development of multiple unconventional T cell lineages whose thymic selection relies on homotypic interactions between hematopoietic cells

    A distal effect of microsomal triglyceride transfer protein deficiency on the lysosomal recycling of CD1d

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    Microsomal triglyceride transfer protein (MTP) is an endoplasmic reticulum (ER)–resident lipid transfer protein involved in the biosynthesis and lipid loading of apolipoprotein B. MTP was recently suggested to directly regulate the biosynthesis of the MHC I–like, lipid antigen presenting molecule CD1d, based on coprecipitation experiments and lipid loading assays. However, we found that the major impact of MTP deficiency occurred distal to the ER and Golgi compartments. Thus, although the rates of CD1d biosynthesis, glycosylation maturation, and internalization from the cell surface were preserved, the late but essential stage of recycling from lysosome to plasma membrane was profoundly impaired. Likewise, functional experiments indicated defects of CD1d-mediated lipid presentation in the lysosome but not in the secretory pathway. These intriguing findings suggest a novel, unexpected role of MTP at a late stage of CD1d trafficking in the lysosomal compartment

    Expansion and long-range differentiation of the NKT cell lineage in mice expressing CD1d exclusively on cortical thymocytes

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    Unlike conventional major histocompatibility complex–restricted T cells, Vα14-Jα18 NKT cell lineage precursors engage in cognate interactions with CD1d-expressing bone marrow–derived cells that are both necessary and sufficient for their thymic selection and differentiation, but the nature and sequence of these interactions remain partially understood. After positive selection mediated by CD1d-expressing cortical thymocytes, the mature NKT cell lineage undergoes a series of changes suggesting antigen priming by a professional antigen-presenting cell, including extensive cell division, acquisition of a memory phenotype, the ability to produce interleukin-4 and interferon-γ, and the expression of a panoply of NK receptors. By using a combined transgenic and chimeric approach to restrict CD1d expression to cortical thymocytes and to prevent expression on other hematopoietic cell types such as dendritic cells, macrophages, or B cells, we found that, to a large extent, expansion and differentiation events could be imparted by a single-cognate interaction with CD1d-expressing cortical thymocytes. These surprising findings suggest that, unlike thymic epithelial cells, cortical thymocytes can provide unexpected, cell type–specific signals leading to lineage expansion and NKT cell differentiation
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