Soluble peptide treatment reverses CD8 T-cell-induced disease in a mouse model of spontaneous tissue-selective autoimmunity.
Soluble peptide treatment reverses CD8 T-cell-induced disease in a mouse model of spontaneous tissue-selective autoimmunity.
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DOI：
10.1038/jid.2011.347
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发表时间：
2012-03
影响因子：
6.5
通讯作者：
Katz, Stephen I.
中科院分区：
文献类型：
--
作者：
Paek, So Yeon;Miyagawa, Fumi;Zhang, Hong;Linton, Jay T.;Hoover, Shelley B.;Simpson, R. Mark;Katz, Stephen I.
自身免疫的转基因（Tg）小鼠模型已被用于表达可被T细胞或自身抗体识别的模型抗原。为了鉴定CD 8介导的组织特异性自身免疫反应的机制并鉴定潜在的治疗方法，我们通过杂交K14-sOVA小鼠产生了自身免疫的双转基因（DTg）小鼠模型，所述小鼠主要在外耳皮肤中表达可溶性鸡卵清蛋白（OVA），OT-I小鼠，其CD 8 T细胞表达T细胞受体的Vα2/Vβ5区，并且对与I类MHC相关的SIINFEKL肽（OVA 257-264）具有特异性。K14-sOVA/OT-I DTg小鼠在生命的前6天内发展选择性靶向外耳道的破坏性过程。耳芽区域出现OT-I细胞的强烈炎性浸润。将SIINFEKL肽i. v.给药于妊娠F1小鼠，随后i. p.给药于新生幼崽，导致外耳发育正常。用这种自身肽处理显著减少OT-I细胞数量以及下调CD 8辅助受体。该模型可用于研究局部的、组织特异性的、免疫介导的皮肤病，并告知我们已知特定分子靶点的自身免疫性疾病的潜在治疗方法。
Transgenic (Tg) mouse models of autoimmunity have been utilized to express model antigens that can be recognized by T cells or by autoantibodies. To identify mechanisms of CD8-mediated tissue-specific autoimmune reactions and to identify potential treatments, we generated a double transgenic (DTg) murine model of autoimmunity by crossing K14-sOVA mice, which express soluble chicken ovalbumin (OVA) predominantly in external ear skin, with OT-I mice whose CD8 T cells express Vα2/Vβ5 regions of the T cell receptor and are specific for SIINFEKL peptide (OVA 257-264) in association with class I MHC. The K14-sOVA/OT-I DTg mice develop a destructive process selectively targeting the external ear pinnae in the first 6 days of life. The ear bud area develops an intense inflammatory infiltrate of OT-I cells. Administration of the SIINFEKL peptide i.v. to pregnant F1 mice and subsequently i.p. to newborn pups resulted in normal external ear development. Treatment with this self-peptide markedly reduced OT-I cell numbers as well as down-regulated the CD8 co-receptor. This model can be useful in studying localized, tissue-specific, immune-mediated skin disease and inform us about potential therapies for autoimmune diseases in which specific molecular targets are known.
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影响因子：
30.5
作者：
McGargill, MA;Derbinski, JM;Hogquist, KA
通讯作者：
Hogquist, KA
影响因子：
4.4
作者：
Bercovici, N;Heurtier, A;Liblau, R
通讯作者：
Liblau, R
影响因子：
30.5
作者：
Park, Jung-Hyun;Adoro, Stanley;Singer, Alfred
通讯作者：
Singer, Alfred
DOI：
10.4049/jimmunol.0900793
发表时间：
2009-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gutermuth J;Nograles KE;Miyagawa F;Nelson E;Cho YH;Katz SI
通讯作者：
Katz SI
影响因子：
6.5
作者：
GOLDBERG, DJ;SABOLINSKI, M;BYSTRYN, JC
通讯作者：
BYSTRYN, JC