Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
J Invest Dermatol. 2013 Mar;133(3):702-711. doi: 10.1038/jid.2012.396. Epub 2012 Nov 29.
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.
在过去的十年中，人们通过使用小鼠接触超敏反应（CHS）模型，深入研究了过敏性接触性皮炎的发病机制。然而，仍然有很大一部分调节机制尚未明确，而这些机制可能适用于过敏性接触性皮炎的治疗。为了确定 B 和 T 淋巴细胞衰减因子（BTLA），一种 CD28 家族共抑制受体，在半抗原诱导的 CHS 中的作用，BTLA 缺陷（BTLA（-/-））小鼠和同窝野生型（WT）小鼠接受二硝基氟苯（DNFB）诱导的 CHS，严重联合免疫缺陷（SCID）小鼠注射 CD4（+）T 细胞，WT 小鼠或 BTLA（-/-）小鼠的 CD8（+）T 细胞接受 CHS。与 WT 小鼠相比，BTLA（-/-）小鼠表现出增强的 DNFB 诱导的 CHS 和 CD8（+）T 细胞的增殖和 IFN-γ产生。与注射 WT CD4（+）T 细胞和 WT CD8（+）T 细胞的 SCID 小鼠相比，注射 WT CD4（+）T 细胞和 BTLA（-/-）CD8（+）T 细胞的 SCID 小鼠表现出更严重的 CHS。另一方面，与注射 WT CD4（+）T 细胞和 WT CD8（+）T 细胞的 SCID 小鼠相比，注射 BTLA（-/-）CD4（+）T 细胞和 WT CD8（+）T 细胞的 SCID 小鼠表现出相似的 CHS。最后，为了评估 BTLA 激动剂对 CHS 的治疗潜力，研究了激动性抗 BTLA 抗体（6A6）对 CHS 的影响。体内注射 6A6 抑制了 DNFB 诱导的 CHS 和 CD8（+）T 细胞的 IFN-γ产生。综上所述，这些结果表明，用激动剂刺激 BTLA 在 CHS 中具有治疗潜力。
