title: Therapeutic potential of B and T lymphocyte attenuator expressed on CD8+ T cells for contact hypersensitivity.
abstract: In the past decade, mechanisms underlying allergic contact dermatitis have been intensively investigated by using contact hypersensitivity (CHS) models in mice. However, the regulatory mechanisms, which could be applicable for the treatment of allergic contact dermatitis, are still largely unknown. To determine the roles of B and T lymphocyte attenuator (BTLA), a CD28 family coinhibitory receptor, in hapten-induced CHS, BTLA-deficient (BTLA(-/-)) mice and littermate wild-type (WT) mice were subjected to DNFB-induced CHS, severe combined immunodeficient (SCID) mice were injected with CD4(+) T cells, and CD8(+) T cells from either WT mice or BTLA(-/-) mice were subjected to CHS. BTLA(-/-) mice showed enhanced DNFB-induced CHS and proliferation and IFN-γ production of CD8(+) T cells as compared with WT mice. SCID mice injected with WT CD4(+) T cells and BTLA(-/-) CD8(+) T cells exhibited more severe CHS as compared with those injected with WT CD4(+) T cells and WT CD8(+) T cells. On the other hand, SCID mice injected with BTLA(-/-) CD4(+) T cells and WT CD8(+) T cells exhibited similar CHS to those injected with WT CD4(+) T cells and WT CD8(+) T cells. Finally, to evaluate the therapeutic potential of an agonistic agent for BTLA on CHS, the effects of an agonistic anti-BTLA antibody (6A6) on CHS were examined. In vivo injection of 6A6 suppressed DNFB-induced CHS and IFN-γ production of CD8(+) T cells. Taken together, these results suggest that stimulation of BTLA with agonistic agents has therapeutic potential in CHS.
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Nakagomi
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address: suzuki_k@faculty.chiba-u.jp.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hosokawa
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Suto
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takatori
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsue
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Yamanashi University, Yamanashi, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address: nakajimh@faculty.chiba-u.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003877:Dermatitis, Contact / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004139:Dinitrofluorobenzene / Q000009:adverse effects; D004195:Disease Models, Animal; D006241:Haptens / Q000009:adverse effects; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D011971:Receptors, Immunologic / Q000819:agonists* / Q000172:deficiency / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000888:Antibodies, Anti-Idiotypic; C488868:BTLA protein, mouse; D006241:Haptens; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene