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B7 Molecules (b7 + molecule)
Selected AbstractsCD8,+ DC are not the sole subset cross-presenting cell-associated tumor antigens from a solid tumorEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2010Alison M. McDonnell Abstract One of the clear paradoxes in tumor immunology is the fact that cross-presentation of cell-associated tumor antigens to CD8+ T cells is efficient, yet CTL generation is weak, and tumors continue to grow. We examined, for the first time whether this may be due to alterations in the phenotype or function of cross-presenting DC using a solid tumor model expressing a membrane bound neo-antigen (hemagglutinin, HA). Tumor antigen was constitutively cross-presented in the tumor-draining LN throughout tumor progression by CD11c+ DC. Further analysis revealed that both CD8,+ and CD8,, DC subsets, but not plasmacytoid DC, were effective at cross-presenting HA tumor antigen. The proportions of DC subsets in the tumor-draining LN were equivalent to those seen in the LN of naïve mice; however, a significant increase in the expression of the potential inhibitory B7 molecule, B7-DC, was noted and appeared to be restricted to the CD8,, DC subset. Therefore LN resident CD8,+ DC are not the sole DC subset capable of cross-presenting cell-associated tumor antigens. Migratory tumor DC subsets with altered co-stimulatory receptor expression may contribute to induction and regulation of tumor-specific responses. [source] NKT cells play critical roles in the induction of oral tolerance by inducing regulatory T cells producing IL-10 and transforming growth factor ,, and by clonally deleting antigen-specific T cellsIMMUNOLOGY, Issue 1 2006Hyun Jung Kim Summary Oral tolerance is the systemic unresponsiveness induced by orally administered proteins. To explore the roles of natural killer T (NKT) cells in oral tolerance, we induced oral tolerance to ovalbumin (OVA) in NKT cell-deficient mice. In CD1d,/, mice, the induction of tolerance to orally administered high- or low-dose OVA was impaired. Dendritic cells (DCs) in the Peyer's patches (PPs) of CD1d,/, mice fed OVA showed high expression of major histocompatibility complex (MHC) class II and B7 molecules, whereas DCs of control mice fed OVA expressed low levels of these molecules. The adoptive transfer of NKT cells restored oral tolerance and induction of tolerogenic DCs in the PPs and spleens of CD1d,/, mice. Moreover, interleukin (IL)-10 and transforming growth factor (TGF)-,1 production in vitro were reduced in cells from the spleen and PPs of CD1d,/, mice compared with those of control mice fed OVA. The numbers of OVA-specific CD4+ KJ1-26+ T cells were significantly reduced in the PPs and spleens of DO11·10 mice fed OVA. In contrast, OVA-specific CD4+ KJ1-26+ T cells were not deleted in the PPs or spleens of DO11·10 CD1d,/, mice. In conclusion, NKT cells were found to play an indispensable role in oral tolerance by inducing regulatory T cells, and clonally deleting antigen-specific CD4+ T cells. [source] The immunological basis of B-cell therapy in systemic lupus erythematosusINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2010Mo Yin MOK Abstract Loss of B-cell tolerance is a hallmark feature of the pathogenesis in systemic lupus erythematosus (SLE), an autoimmune disease that is characterized by hypergammaglobulinemia and autoantibody production. These autoantibodies lead to formation of immune-complex deposition in internal organs causing inflammation and damage. Autoreactive B-cells are believed to be central in the pathophysiology of SLE. Other than its role in the production of antibodies that mediate humoral immune response, B-cells also function as antigen-presenting cells and are capable of activating T-cells. Activated B-cells may also produce pro-inflammatory cytokines that aggravate local inflammation. Abnormal B-cell homeostasis has been described in SLE patients. This may occur as a result of intrinsic B-cell defect or from aberrant regulation by maturation and survival signals. B-cell-based therapy is the current mainstream of research and development of novel therapies in SLE patients with severe and refractory disease. Potential cellular and molecular targets for B-cell therapies include cell surface molecules such as CD20 (rituximab) and CD22 (epratuzumab); co-stimulatory molecules involved in B-cell,T-cell interaction such as CTLA4 and B7 molecules (abatacept); maturation and growth factors such as B-cell activating factor and a proliferation-inducing ligand (belimumab, briobacept, atacicept) and B-cell tolerogen (abetimus). This article provides an overview on normal B-cell physiology and abnormal B-cell biology in SLE that form the immunological basis of B-cell-targeted therapy in the treatment of these patients with refractory diseases. [source] Enhanced B7 Costimulatory Molecule Expression In Inflammatory Human Sural Nerve BiopsiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001R Kiefer Objectives-To define the role of the costimulatory molecules B7-1 and B7-2 in inflammatory disorders of the peripheral nervous system. B7 molecules are essential for effective antigen presentation and may determine the differentiation of T cells into a Th-1 or Th-2 phenotype, thus modulating immune response and disease course. Methods-Forty nine sural nerve biopsies from patients with neuroborreliosis, Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), CIDP variants and hereditary neuropathies, and those with no detectable abnormality were investigated. The expression of B7-1 and B7-2 mRNA and protein was investigated by polymerase chain reaction (PCR) and immunocytochemistry. Results-B7-1 mRNA was strongly upregulated in both cases of neuroborreliosis, in two cases of GBS and one case of variant CIDP. Moderate to low levels were detected in the remaining GBS and CIDP biopsies and were rarely found in a noninflammatory control group consisting of hereditary neuropathy and normal nerves. At the immunocytochemical level, strong expression of B7-1 protein was found in both neuroborreliosis cases, and moderate or low expression in six of eight GBS cases and seven of 17 CIDP cases investigated, whereas only one of five non-inflammatory control nerves showed staining, which was very weak. In neuroborreliosis, B7-1 protein was found very pronounced in epineurial infiltrates, whereas in CBS and CIDP, labelling was predominantly endoneurial and localised to putative macrophages. B7-2 mRNA and protein were expressed only at low levels in neuroborreliosis and selected autoimmune neuropathy cases, and were essentially absent from noninflammatory controls. Conclusions-B7 molecules are expressed in the peripheral nervous system and regulated during disease, and their presence in macrophages underlines the putative function of endoneurial macrophages as local antigen presenting cells in the immunopathology of peripheral nerve. B7-1 rather than B7-2 is preferentially upregulated, possibly promoting the induction of a Th-1-type T cell response within the nerve. [source] | ||||||||||