Galectin-9 Controls CD40 Signaling through a Tim-3 Independent Mechanism and Redirects the Cytokine Profile of Pathogenic T Cells in Autoimmunity

While it has long been understood that CD40 plays a critical role in the etiology of autoimmunity, glycobiology is emerging as an important contributor. CD40 signaling is also gaining further interest in transplantation and cancer therapies. Work on CD40 signaling has focused on signaling outcomes and blocking of its ligand, CD154, while little is known about the actual receptor itself and its control. We demonstrated that CD40 is in fact several receptors occurring as constellations of differentially glycosylated forms of the protein that can sometimes form hybrid receptors with other proteins. An enticing area of autoimmunity is differential glycosylation of immune molecules leading to altered signaling. Galectins interact with carbohydrates on proteins to effect such signaling alterations. Studying autoimmune prone NOD and non-autoimmune BALB/c mice, here we reveal that in-vivo CD40 signals alter the glycosylation status of non-autoimmune derived CD4 T cells to resemble that of autoimmune derived CD4 T cells. Galectin-9 interacts with CD40 and, at higher concentrations, prevents CD40 induced proliferative responses of CD4loCD40+ effector T cells and induces cell death through a Tim-3 independent mechanism. Interestingly, galectin-9, at lower concentrations, alters the surface expression of CD3, CD4, and TCR, regulating access to those molecules and thereby redirects the inflammatory cytokine phenotype and CD3 induced proliferation of autoimmune CD4loCD40+ T cells. Understanding the dynamics of the CD40 receptor(s) and the impact of glycosylation status in immunity will gain insight into how to maintain useful CD40 signals while shutting down detrimental ones

Antibodies against cell surface antigens as very potent immunological adjuvants

We describe here two very potent adjuvant systems which are thought to work directly on antigen specific lymphocytes, thus by-passing the normal route for adjuvants, which is to activate antigen presenting cells (APCs) inducing release of inflammatory cytokines with resultant side effects of local and systemic reactogenicity. CD40 and CD28 based adjuvants are extremely potent and should avoid the inflammatory side effects induced by most adjuvants

Antibodies against cell surface antigens as very potent immunological adjuvants

We describe here two very potent adjuvant systems which are thought to work directly on antigen specific lymphocytes, thus by-passing the normal route for adjuvants, which is to activate antigen presenting cells (APCs) inducing release of inflammatory cytokines with resultant side effects of local and systemic reactogenicity. CD40 and CD28 based adjuvants are extremely potent and should avoid the inflammatory side effects induced by most adjuvants

FPGA Acceleration of Communication-Bound Streaming Applications: Architecture Modeling and a 3D Image Compositing Case Study

Reconfigurable computers usually provide a limited number of different memory resources, such as host memory, external memory, and on-chip memory with different capacities and communication characteristics. A key challenge for achieving high-performance with reconfigurable accelerators is the efficient utilization of the available memory resources. A detailed knowledge of the memories' parameters is key for generating an optimized communication layout. In this paper, we discuss a benchmarking environment for generating such a characterization. The environment is built on IMORC, our architectural template and on-chip network for creating reconfigurable accelerators. We provide a characterization of the memory resources available on the XtremeData XD1000 reconfigurable computer. Based on this data, we present as a case study the implementation of a 3D image compositing accelerator that is able to double the frame rate of a parallel renderer

Oral Immunization with Recombinant Mycobacterium smegmatis Expressing the Outer Membrane Protein 26-Kilodalton Antigen Confers Prophylactic Protection against Helicobacter pylori Infection ▿ †

Helicobacter pylori infection is prevalent worldwide and results in chronic gastritis, which may lead to gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. We have previously reported that oral immunization with recombinant Mycobacterium smegmatis expressing the H. pylori outer membrane protein 26-kilodalton (Omp26) antigen affords therapeutic protection against H. pylori infection in mice. In the present study, we investigated the prophylactic effects of this vaccine candidate on H. pylori challenge in mice. We found that oral immunization with recombinant Mycobacterium Omp26 significantly reduced H. pylori colonization in the stomach compared to inoculation with wild-type M. smegmatis in control mice. Six of the recombinant Mycobacterium-immunized mice (60%) were completely protected from H. pylori infection. The severity of H. pylori-associated chronic gastritis assessed histologically was significantly milder in mice vaccinated with recombinant Mycobacterium than in control animals. Mice immunized with recombinant Mycobacterium showed enhanced antigen-specific lymphocyte proliferation and antibody responses. Moreover, immunization with recombinant Mycobacterium resulted in an increased expression of interleukin-2 and gamma interferon in the stomach and spleen, as determined by reverse transcription-PCR analysis. Our results collectively suggest that vaccination with recombinant Mycobacterium Omp26 confers prophylactic protection against H. pylori infection. The inhibition of H. pylori colonization is associated with the induction of antigen-specific humoral and cell-mediated immune responses