title: Co-stimulation with TNF receptor superfamily 4/25 antibodies enhances in-vivo expansion of CD4+CD25+Foxp3+ T cells (Tregs) in a mouse study for active DNA Aβ42 immunotherapy.
abstract: The study was designed to test DNA Aβ42 immunization in mice as alternative approach for possible active immunotherapy in Alzheimer patients. As results, we found polarized Th2 immune responses, efficient Aβ42 antibody levels, and disappearance of antigen specific T cells. In-vivo TNFRSF4/25 antibody co-stimulation enhanced Aβ42 specific T cell responses with initial Th2 expansion and subsequent development of Aβ42 specific CD4+CD25+Foxp3+ cells. It showed that Th2 biased responses due to gene gun immunizations propagate the development of regulatory T cells. In conclusion, full-length DNA Aβ42 immunization into skin results in a regulatory response with minimal risk of inflammation and autoimmunity.
authors.affiliation: Department of Neurology and Neurotherapeutics, Alzheimer's Disease Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: doris.lambracht-washington@utsouthwestern.edu.
authors.forename: Doris
authors.initials: D
authors.lastname: Lambracht-Washington
authors.affiliation: Department of Neurology and Neurotherapeutics, Alzheimer's Disease Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Roger N
authors.initials: RN
authors.lastname: Rosenberg
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology; D053262:Receptors, OX40 / Q000276:immunology*; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D016207:Cytokines; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D010446:Peptide Fragments; D053262:Receptors, OX40; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506034:Tnfrsf25 protein, mouse; C505717:Tnfrsf4 protein, mouse; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse; C075222:amyloid beta-protein (1-42); D004247:DNA
keywords: Alzheimer disease; DNA Aβ42 immunization; Skin immunity; TNFRSF4/25 antibody co-stimulation; Th2/Treg differentiation