ABSTRACT
Chemokine receptors are differentially expressed on immature and mature dendritic cells (DC). Herein, we demonstrate for the first time that murine antimicrobial peptides beta-defensins 2 and 3 bind murine CCR6, similarly to inflammatory chemokine macrophage-inflammatory protein 3alpha, and they chemoattract bone marrow-derived immature, but not mature DC. Using various chemokines or defensins fused with nonimmunogenic tumor Ags, we studied their capacity to delivery Ags to subsets of immune cells to elicit antitumor immunity. We demonstrate that DNA immunizations with fusion constructs with beta-defensin 2 or inflammatory chemokines that target immature DC, but not homeostatic chemokines secondary lymphoid tissue chemokine, CCL21, or stromal cell-derived factor 1, CXCL12, which chemoattract mature DC, elicit humoral, protective, and therapeutic immunity against two different syngeneic lymphomas.
Subject(s)
Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Dendritic Cells/cytology , Dendritic Cells/immunology , Immunotherapy, Adoptive/methods , Lymphoma, B-Cell/immunology , Lymphoma, B-Cell/therapy , Vaccines, DNA/immunology , Animals , Antibodies, Anti-Idiotypic/biosynthesis , Antibodies, Anti-Idiotypic/genetics , Cancer Vaccines/administration & dosage , Cancer Vaccines/genetics , Cancer Vaccines/immunology , Cell Differentiation/genetics , Cell Differentiation/immunology , Cell Line , Chemokines/administration & dosage , Chemokines/genetics , Chemokines/immunology , Chemokines/physiology , Female , Gene Targeting , Humans , Immunity, Innate/genetics , Immunoglobulin Variable Region/administration & dosage , Immunoglobulin Variable Region/genetics , Immunoglobulin Variable Region/immunology , Lymphoma, B-Cell/genetics , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Receptors, Chemokine/genetics , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/chemical synthesis , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/physiology , Tumor Cells, Cultured , Vaccines, DNA/administration & dosage , Vaccines, DNA/genetics , beta-Defensins/administration & dosage , beta-Defensins/genetics , beta-Defensins/immunology , beta-Defensins/physiologyABSTRACT
This paper presents an initial assessment of the Children's Attributional Style Interview (CASI), a newly designed measure for assessing attributional style in young children (age 5 and up). The CASI was used to conduct prospective tests of the reformulated helplessness and the integrated hopelessness/self-esteem theories of depression in a sample of 147 5-10-year-old children. For comparison, the same tests were also conducted with the Children's Attributional Style Questionnaire-Revised, a commonly used measure for assessing attributional style in older children (age 8 and up). The CASI evidenced support of the reformulated helplessness theory and partial support of the integrated hopelessness/self-esteem theory. The CASI also demonstrated good internal consistency. Thus, our findings provide initial support for the CASI as a methodologically sound measure of attributional style for children as young as 5 years old. Although preliminary, our findings also suggest possible developmental differences in how attributional style interacts with self-esteem and negative life stress. The CASI should prove to be a useful tool in furthering the understanding of the origins and development of attributional style in childhood, as well as its contribution to the understanding of the development and prevention of depressive symptomatology in children.
