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IN THIS ISSUE
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The Phenotype Of Human Th17 Cells And Their Precursors, The Cytokines That Mediate Their Differentiation And The Role Of Th17 Cells In Inflammation
T helper 17 (Th17) cells represent a new subset of CD4+ effector T cells which have been described in both mice and humans. However, some differences seem to exist between murine and human Th17 cells with regard to their features, origin and role in immunopathology. Murine Th17 cells share their developmental origin with Foxp3+ Treg cells, indeed naive T-cell precursors can be differentiated to re...

Immunomodulation Of Human B Cells Following Treatment With Intravenous Immunoglobulins Involves Increased Phosphorylation Of Extracellular Signal-regulated Kinases 1 And 2
In the treatment of autoimmune diseases, intravenous Igs (IVIg) are assumed to modulate immune cells through the binding of surface receptors. IVIg act upon definite human B cell populations to modulate Ig repertoire, and such modulation might proceed through intracellular signaling. However, the heterogeneity of human B cell populations complicates investigations of the intracellular pathways inv...

Single-strand DNA Breaks In Ig Class Switch Recombination That Depend On UNG But Not AID
B lymphocytes switch from secreting IgM to secreting IgG, IgA or IgE through a DNA recombination, class switch recombination (CSR), whose mechanism is incompletely understood. CSR is thought to be triggered by activation-induced deaminase (AID), which is believed to deaminate cytosines to uracil in single-strand regions of switch region DNA. Subsequent excision of uracils by uracil DNA glycosylase...

Regulatory Role Of NKp44, NKp46, DNAM-1 And NKG2D Receptors In The Interaction Between NK Cells And Trophoblast Cells. Evidence For Divergent Functional Profiles Of Decidual Versus Peripheral NK Cells
During the first trimester of pregnancy NK cells represent >50% of the lymphoid cells present in the human decidua where they reside in close contact with trophoblast cells. Because in decidual tissues NK cell activation and function may be induced by this interaction, we analyzed the cellular ligands recognized by activating NK receptors expressed on trophoblast cells. We show that these cells...

A Single Base Mutation In The PRAT4A Gene Reveals Differential Interaction Of PRAT4A With Toll-like Receptors
Toll-like receptors (TLRs) play an essential role in defense responses. Immune cells express multiple TLRs which are simultaneously activated by microbial pathogens. PRotein Associated with Tlr4 A (PRAT4A) is a chaperone-like endoplasmic reticulum (ER)-resident protein required for the proper subcellular distribution of multiple TLRs. PRAT4A–/– mice show impaired expression of TLR2/4 o...

PKC{eta} Directs Induction Of IRF-4 Expression And Ig {kappa} Gene Rearrangement In Pre-BCR Signaling Pathway
Pre-B cell receptor (pre-BCR) signals promote pre-B cell differentiation, in which the adaptor protein B-cell linker (BLNK) plays a crucial role. However, the molecular pathways downstream of BLNK are currently unclear. Utilizing pre-B leukemia cell lines (BKO84 and others) derived from BLNK-deficient mice as in vitro models of the pre-B cell differentiation, we have demonstrated that reconstituti...

Impaired TCR Signaling Through Dysfunction Of Lipid Rafts In Sphingomyelin Synthase 1 (SMS1)-knockdown T Cells
During T cell activation, TCRs cluster at the center of the T cell–antigen-presenting cell interface forming the central supramolecular activation cluster. Although it has been suggested that sphingolipid- and cholesterol-rich microdomains, termed lipid rafts, form platforms for the regulation and transduction of TCR signals, an actual role for membrane sphingomyelin (SM), a key component of...

Activation And Control Of Pathogenic T Cells In OSP/claudin-11-induced EAE In SJL/J Mice Are Dominated By Their Focused Recognition Of A Single Epitopic Residue (OSP58M)
Oligodendrocyte-specific protein (OSP)/claudin-11 has been recently implicated in multiple sclerosis pathophysiology. Yet, the pathogenic autoimmunity against OSP has been poorly investigated. We previously showed that OSP-induced experimental autoimmune encephalomyelitis (EAE) and optic neuritis in SJL/J mice are primarily associated with CD4+ T cells reactive against OSP55-80. Dissecting the fin...

Mass Spectrometric Identification Of An HLA-A*0201 Epitope From Plasmodium Falciparum MSP-1
Cytotoxic T lymphocytes (CTL) directed against Plasmodium falciparum-derived antigens were shown to play an important role for the protection against malaria. Although several CTL epitopes have been identified from P. falciparum sporozoite-derived antigens, none has been described for the merozoite form. Since the merozoite surface protein (MSP)-1 is a known target of the immune response, we focus...

Methylation Of CIITA Promoter IV Causes Loss Of HLA-II Inducibility By IFN-{gamma} In Promyelocytic Cells
The human promyelocytic cell line THP-1 expresses high level of HLA class II (HLA-II) molecules after IFN- treatment. Here, we report a variant of THP-1 that does not express HLA-II after IFN-. The variant's HLA-II phenotype is constant over time in culture and it is not related to a defective IFN--signalling pathway. Transfection of CIITA, the HLA-II transcriptional activator, under the control o...

Deliberately Provoking Local Inflammation Drives Tumors To Become Their Own Protective Vaccine Site
Anti-cancer immunotherapies aim to generate resolution of all existing tumors, including inaccessible ones, and provide long-term protection against recurrence. This is rarely achieved. Thus, we aimed to determine if the tumor microenvironment could be turned into a potent ‘self’-vaccine site. Our target was to eradicate larger tumor burdens. Our models respond to single-agent immunoth...

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