Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood.
Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood.
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DOI：
10.1084/jem.20130592
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发表时间：
2013-08-26
期刊：
影响因子：
--
通讯作者：
Casanova JL
中科院分区：
文献类型：
--
作者：
Byun M;Ma CS;Akçay A;Pedergnana V;Palendira U;Myoung J;Avery DT;Liu Y;Abhyankar A;Lorenzo L;Schmidt M;Lim HK;Cassar O;Migaud M;Rozenberg F;Canpolat N;Aydogan G;Fleckenstein B;Bustamante J;Picard C;Gessain A;Jouanguy E;Cesarman E;Olivier M;Gros P;Abel L;Croft M;Tangye SG;Casanova JL
人OX 40是强大的CD 4 + T细胞记忆所必需的，并在内皮细胞中赋予针对HHV-8感染的选择性保护性免疫。卡波西肉瘤（KS）是一种人类疱疹病毒8（HHV-8;也称为KSHV）诱导的内皮肿瘤，仅在一小部分感染HHV-8的个体中发生。我们推测，先天性免疫缺陷HHV-8可能是导致儿童时期非常罕见的经典KS发展的基础。我们在这里报告常染色体隐性OX 40缺乏症在其他健康成人儿童发病的经典KS。0X 40是在活化的T细胞上表达的共刺激受体。其配体OX 40 L在多种细胞类型上表达，包括内皮细胞。我们发现OX 40 L在KS病变中大量表达。突变型OX 40蛋白在细胞表面表达不足，不能结合OX 40 L，导致完全功能性OX 40缺陷。患者外周血中效应记忆CD 4 + T细胞比例较低，与体外回忆抗原的CD 4 + T细胞应答受损一致。效应记忆CD 8 + T细胞的比例减少较少。循环记忆B细胞的比例很低，但体内抗体反应是完整的，包括对疫苗加强的反应。总之，这些发现表明，人OX 40是强大的CD 4 + T细胞记忆所必需的，并赋予内皮细胞对HHV-8感染的明显选择性保护性免疫。
Human OX40 is necessary for robust CD4+ T cell memory and confers selective protective immunity against HHV-8 infection in endothelial cells. Kaposi sarcoma (KS), a human herpes virus 8 (HHV-8; also called KSHV)–induced endothelial tumor, develops only in a small fraction of individuals infected with HHV-8. We hypothesized that inborn errors of immunity to HHV-8 might underlie the exceedingly rare development of classic KS in childhood. We report here autosomal recessive OX40 deficiency in an otherwise healthy adult with childhood-onset classic KS. OX40 is a co-stimulatory receptor expressed on activated T cells. Its ligand, OX40L, is expressed on various cell types, including endothelial cells. We found OX40L was abundantly expressed in KS lesions. The mutant OX40 protein was poorly expressed on the cell surface and failed to bind OX40L, resulting in complete functional OX40 deficiency. The patient had a low proportion of effector memory CD4+ T cells in the peripheral blood, consistent with impaired CD4+ T cell responses to recall antigens in vitro. The proportion of effector memory CD8+ T cells was less diminished. The proportion of circulating memory B cells was low, but the antibody response in vivo was intact, including the response to a vaccine boost. Together, these findings suggest that human OX40 is necessary for robust CD4+ T cell memory and confers apparently selective protective immunity against HHV-8 infection in endothelial cells.
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DOI：
10.1002/mpo.10078
发表时间：
2002-08-01
期刊：
MEDICAL AND PEDIATRIC ONCOLOGY
影响因子：
--
作者：
Ferrari, A;Casanova, M;Carli, M
通讯作者：
Carli, M
DOI：
10.1084/jem.20101597
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Byun M;Abhyankar A;Lelarge V;Plancoulaine S;Palanduz A;Telhan L;Boisson B;Picard C;Dewell S;Zhao C;Jouanguy E;Feske S;Abel L;Casanova JL
通讯作者：
Casanova JL
影响因子：
5.1
作者：
Camcioglu, Y;Picard, C;Casanova, JL
通讯作者：
Casanova, JL
影响因子：
10.3
作者：
Davidovici, B;Karakis, I;Boshoff, C
通讯作者：
Boshoff, C
影响因子：
20.3
作者：
Duhen, Thomas;Duhen, Rebekka;Campbell, Daniel J.
通讯作者：
Campbell, Daniel J.