Induction of autoimmunity by expansion of autoreactive CD4+CD62Llow cells in vivo.
Journal - Journal of immunology (Baltimore, Md. : 1950) (United States )
The prerequisites of peripheral activation of self-specific CD4(+) T cells that determine the development of autoimmunity are incompletely understood. SJL mice immunized with myelin proteolipid protein (PLP) 139-151 developed experimental autoimmune encephalomyelitis (EAE) when pertussis toxin (PT) was injected at the time of immunization but not when injected 6 days later, indicating that PT-induced alterations of the peripheral immune response lead to the development of autoimmunity. Further analysis using IA(s)/PLP(139-151) tetramers revealed that PT did not change effector T cell activation or regulatory T cell numbers but enhanced IFN-gamma production by self-specific CD4(+) T cells. In addition, PT promoted the generation of CD4(+)CD62L(low) effector T cells in vivo. Upon adoptive transfer, these cells were more potent than CD4(+)CD62L(high) cells in inducing autoimmunity in recipient mice. The generation of this population was paralleled by higher expression of the costimulatory molecules CD80, CD86, and B7-DC, but not B7-RP, PD-1, and B7-H1 on CD11c(+)CD4(+) dendritic cells whereas CD11c(+)CD8alpha(+) dendritic cells were not altered. Collectively, these data demonstrate the induction of autoimmunity by specific in vivo expansion of CD4(+)CD62L(low) cells and indicate that CD4(+)CD62L(low) effector T cells and CD11c(+)CD4(+) dendritic cells may be attractive targets for immune interventions to treat autoimmune diseases.
|ISSN : ||0022-1767|
|Mesh Heading : ||Adjuvants, Immunologic Adoptive Transfer Animals Antigens, CD11c Antigens, CD80 Antigens, CD86 CD4-Positive T-Lymphocytes Cell Differentiation Dendritic Cells Encephalomyelitis, Autoimmune, Experimental Flow Cytometry L-Selectin Lymphocyte Activation Mice Myelin Proteolipid Protein Peptide Fragments Pertussis Toxin immunology metabolism immunology metabolism immunology metabolism cytology immunology cytology immunology immunology immunology immunology immunology immunology|
|Mesh Heading Relevant : ||Autoimmunity Immune Tolerance immunology immunology metabolism|
Economic aspects of bladder cancer: what are the benefits and costs?
Journal - World Journal of Urology
ObjectiveBladder cancer (BC) has the highest lifetime treatment costs per patient of all cancers. The high recurrence rate and ongoing invasive monitoring requirement are the key contributors to the economic and human toll of this disease. The purpose of this paper was to utilize the recent literature to identify opportunities for improving the benefits and costs of BC care.MethodsA PubMed search was performed of recent publications concerning (BC) cost-effectiveness. We reviewed studies, reviews, opinion papers and cost-effectiveness analyses, focusing primarily on non-muscle-invasive bladder cancer (Ta/T1; NMIBC).ResultsNew diagnostic tools such as urine markers may assist in more cost-effectively detecting BC at an earlier stage, however, these markers cannot replace the cystoscopy, which is the current standard of care. A photodynamic diagnostic tool (PDD) using hexylaminolevulinate (Hexvix®) enhances tumor visibility and improves transurethral resection of bladder cancer (TURB) results, potentially reducing recurrence rates and lowering treatment costs. While the importance of BC research has been acknowledged, research investment has been continuously reduced during the last 5 years.ConclusionsThe economic burden of BC is well-characterized in the literature. This study suggests that new technologies (i.e., urine-based tests, PDD) and therapeutic regimes (intravesical chemotherapy, adjuvant immunotherapy) have significant potential to improve the diagnosis, treatment and on-going monitoring of BC patients, with potential improvements in clinical outcomes and concurrent cost-savings. A renewed interest and investment in BC research are required to ensure future advancements.
|ISSN : ||0724-4983|
|Keywords : ||Bladder cancer,Diagnosis and treatment,Fluorescence cystoscopy,Imaging technology,Economic and cost considerations,Intravesical chemotherapy,TURB,PDD,NIMBC,Hexvix|