title: Cytotoxic T lymphocyte antigen 4 immunogloblin promotes neuronal differentiation in the grafts of embryonic stem cell-derived neural precursor cells.
abstract: For safe and efficient transplantation of embryonic stem cells (ESCs), it is important to reduce inflammatory and immune response by the host brain. Full activation of T cells in response to donor antigen requires the delivery of two separate but complimentary signals not only via T cell receptor following recognition of antigen, but also via antigen-nonspecific ligation of the costimulatory receptor-ligand pairs such as CD28:CD80/86. Cytotoxic T lymphocyte antigen 4 (CTLA4), structurally related to CD28, delivers an inhibitory signal after ligation to CD80/86, resulting in the termination of T cell immune responses. To investigate the role of this pathway in the survival and differentiation of neural progenitor cells (NPCs) from mouse ESCs, we transplanted the NPCs into mouse brains with or without CTLA4 immunogloblin (CTLA4-Ig). Immunohistochemical studies revealed that accumulation of inflammatory/immune cells in and around the graft was reduced by CTLA4-Ig. In contrast, the percentage of neurons in the graft was increased. These results suggest that CTLA4-Ig may promote neuronal differentiation during the treatment of neurological diseases with cell replacement therapy.
authors.affiliation: Department of Neurosurgery, Kyoto University, Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shinoyama
authors.forename: M
authors.initials: M
authors.lastname: Ideguchi
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: D
authors.initials: D
authors.lastname: Doi
authors.forename: N
authors.initials: N
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D003470:Culture Media; D053595:Embryonic Stem Cells / Q000276:immunology / Q000502:physiology* / Q000637:transplantation*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000276:immunology / Q000502:physiology* / Q000637:transplantation*; D009474:Neurons / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
chemical_list: D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D003470:Culture Media; D016271:Proto-Oncogene Proteins c-myc