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Adjuvant Properties (adjuvant + property)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Pertussis toxin activates adult and neonatal naive human CD4+ T,lymphocytes

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006
Sandrine Tonon
Abstract Pertussis toxin (PTX) is known to be mitogenic for T,lymphocytes, but its direct action on naive human T cells has not been specified. Herein, we show that PTX induces the proliferation of purified adult CD45RA+CD4+ T cells independently of its ADP-ribosyltransferase activity. PTX directly induces TNF-, and IL-2 mRNA expression, modulates the level of several cell surface receptors and induces Forkhead box,p3 (Foxp3) protein accumulation in naive CD4+ T cells. Addition of autologous dendritic cells was found to be required for the production of high levels of IFN-, by PTX-stimulated naive T cells. These effects of PTX occurred in conjunction with activation of NF-,B and NFAT transcription factors. Overall, responses of neonatal CD4+ T cells to PTX were similar to those of adult CD45RA+CD4+ naive T cells except for their blunted CD40 ligand up-regulation. We suggest that the adjuvant properties of PTX during primary cell-mediated immune responses involve a direct action on naive T,lymphocytes in addition to activation of antigen-presenting cells. [source]

Timing and tuning of CD27,CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathology

IMMUNOLOGICAL REVIEWS, Issue 1 2009
Martijn A. Nolte
Summary:, After binding its natural ligand cluster of differentiation 70 (CD70), CD27, a tumor necrosis factor receptor (TNFR)-associated factor-binding member of the TNFR family, regulates cellular activity in subsets of T, B, and natural killer cells as well as hematopoietic progenitor cells. In normal immune responses, CD27 signaling appears to be limited predominantly by the restricted expression of CD70, which is only transiently expressed by cells of the immune system upon activation. Studies performed in CD27-deficient and CD70-transgenic mice have defined a non-redundant role of this receptor,ligand pair in shaping adaptive T-cell responses. Moreover, adjuvant properties of CD70 have been exploited for the design of anti-cancer vaccines. However, continuous CD27,CD70 interactions may cause immune dysregulation and immunopathology in conditions of chronic immune activation such as during persistent virus infection and autoimmune disease. We conclude that optimal tuning of CD27,CD70 interaction is crucial for the regulation of the cellular immune response. We provide a detailed comparison of costimulation through CD27 with its closely related family members 4-1BB (CD137), CD30, herpes virus entry mediator, OX40 (CD134), and glucocorticoid-induced TNFR family-related gene, and we argue that these receptors do not have a unique function per se but that rather the timing, context, and intensity of these costimulatory signals determine the functional consequence of their activity. [source]

Toll-like receptors , sentries in the B-cell response

IMMUNOLOGY, Issue 3 2009
Isabelle Bekeredjian-Ding
Summary Toll-like receptors (TLR) play a central role in the initiation of the innate immune response to pathogens. Upon recognition of molecular motifs specific for microbial molecules TLR mediate pro-inflammatory cytokine secretion and enhance antigen presentation; in B cells they further promote expansion, class switch recombination and immunoglobulin secretion. As a result of their adjuvant properties, TLR ligands have become an integral component of antimicrobial vaccines. In spite of this, little is known of the direct effects of TLR engagement on B-lymphocyte function. The scope of this review is to outline the differences in TLR expression and reactivity in murine and human B-cell subsets and to provide an overview of the currently available literature. We will further discuss the possible roles of TLR in regulating B-cell effector functions and shaping antibody-mediated defence against microbial pathogens in vivo. [source]

Aluminium per se and in the anti-acid drug sucralfate promotes sensitization via the oral route

ALLERGY, Issue 6 2009
R. Brunner
Background:, Aluminium (ALUM) is used as experimental and clinical adjuvant for parenteral vaccine formulation. It is also contained in anti-acid drugs like sucralfate (SUC). These anti-acids have been shown to cause sensitization to food proteins via elevation of the gastric pH. The aim of this study was to assess the oral adjuvant properties of ALUM, alone or contained in SUC, in a BALB/c mouse model. Methods:, Mice were fed SUC plus ovalbumin (OVA) and compared with groups where ALUM or proton pump inhibitors (PPI) were applied as adjuvants. The humoral and cellular immune responses were assessed on antigen-specific antibody and cytokine levels. The in vivo relevance was investigated in skin tests. Results:, The highest OVA-specific immunoglobulin G1 (IgG1) and IgE antibody levels were found in mice fed with OVA/SUC, followed by OVA/ALUM-treated animals, indicating a T helper 2 (Th2) shift in both groups. Antibody levels in other groups revealed lower (OVA/PPI-group) or baseline levels (control groups). Positive skin tests confirmed an allergic response in anti-acid or adjuvant-treated animals. Conclusions:, Our data show for the first time that ALUM acts as a Th2-adjuvant via the oral route. This suggests that orally applied SUC leads to an enhanced risk for food allergy, not only by inhibiting peptic digestion but also by acting as a Th2-adjuvant by its ALUM content. [source]