ABSTRACT
Increased interest in, and demand for, music therapy provision for persons with dementia prompted this study's exploration of music therapists' strategies for creating musical communities in dementia care settings, considering the needs and resources of people affected by dementia. Focus group discussions and detailed iterative study of improvisational music therapy work by six experienced practitioners clarify the contextual immediacy and socio-musical complexities of music therapy in dementia care homes. Music therapy's 'ripple effect', with resonances from micro (person-to-person musicking), to meso (musicking beyond 'session time') and macro level (within the care home and beyond), implies that all who are part of the dementia care ecology need opportunities for flourishing, shared participation, and for expanded self-identities; beyond 'staff', 'residents', or 'being in distress'. On such basis, managers and funders might consider an extended brief for music therapists' roles, to include generating and maintaining musical wellbeing throughout residential care settings.
Subject(s)
Dementia/therapy , Music Therapy/methods , Communication , Focus Groups , Homes for the Aged , HumansABSTRACT
It has been speculated that autoimmune diseases are caused by failure of central tolerance. However, this remains controversial. We have suggested that CD40 expression identifies autoaggressive T cells in the periphery of autoimmune prone mice. In this study, we report that CD40 was cloned from autoaggressive T cells and that engagement induces expression and nuclear translocation of the recombinases, recombination activating gene (RAG) 1 and RAG2 in the autoaggressive, but not in the nonautoaggressive, peripheral T cell population. Furthermore, we demonstrate that CD40 engagement induces altered TCR Valpha, but not Vbeta, expression in these cells. Therefore, CD40-regulated expression of RAG1 and RAG2 in peripheral T cells may constitute a novel pathway for the generation of autoaggressive T cells.
Subject(s)
Autoimmune Diseases/immunology , CD40 Antigens/physiology , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Gene Expression Regulation/immunology , Genes, RAG-1/immunology , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/immunology , Animals , Autoimmune Diseases/genetics , CD40 Antigens/genetics , Cell Differentiation/genetics , Cell Differentiation/immunology , Clone Cells , Cloning, Molecular , DNA, Complementary/isolation & purification , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Female , Genes, T-Cell Receptor alpha/genetics , Genes, T-Cell Receptor beta/genetics , Mice , Mice, Inbred NOD , RNA, Messenger/biosynthesis , RNA, Messenger/isolation & purification , Receptors, Antigen, T-Cell, alpha-beta/biosynthesis , Receptors, Antigen, T-Cell, alpha-beta/genetics , Signal Transduction/genetics , Signal Transduction/immunology , Spleen/cytology , Spleen/immunology , Spleen/metabolism , T-Lymphocyte Subsets/metabolismABSTRACT
Juvenile diabetes (type 1) is an autoimmune disease in which CD4(+) T cells play a major role in pathogenesis characterized by insulitis and beta cell destruction leading to clinical hyperglycemia. To date, no marker for autoimmune T cells has been described, although it was previously demonstrated that autoimmune mice have a large population of CD4(+) cells that express CD40. We show here that established, diabetogenic T cell clones of either the Th1 or Th2 phenotype are CD40-positive, whereas nondiabetogenic clones are CD40-negative. CD40 functionally signals T cell clones, inducing rapid activation of the transcription factor NFkappaB. We show that autoimmune diabetes-prone nonobese diabetic mice have high levels of CD40(+)CD4(+) T cells in the thymus, spleen, and importantly, in the pancreas. Finally, as demonstrated by adoptive transfers, CD4(+)CD40(+) cells infiltrate the pancreatic islets causing beta-cell degranulation and ultimately diabetes.
