A CD8α- Subset of CD4+SLAMF7+ Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment.
A CD8α- Subset of CD4+SLAMF7+ Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment.
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DOI：
10.1002/art.40469
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Manfredi AA
中科院分区：
文献类型：
--
作者：
Della-Torre E;Bozzalla-Cassione E;Sciorati C;Ruggiero E;Lanzillotta M;Bonfiglio S;Mattoo H;Perugino CA;Bozzolo E;Rovati L;Arcidiacono PG;Balzano G;Lazarevic D;Bonini C;Falconi M;Stone JH;Dagna L;Pillai S;Manfredi AA
非常规的CD 4 + SLAMF 7+细胞毒性TEM细胞（CD 4 + CTL）群体与IgG 4相关疾病（IgG 4-RD）有因果关系。糖皮质激素代表IgG 4-RD患者的一线治疗方法，但其在这种特定疾病中的作用机制仍未知。在这里，我们描述了糖皮质激素对IgG 4-RD中CD 4 + CTL的影响。在基线和糖皮质激素治疗6个月后，通过流式细胞术对18例活动性IgG 4-RD患者的CD 45 RO（TEM）和CD 45 RA（TEMRA）CD 4 + T细胞的效应/记忆区室中的CD 8 α、颗粒酶A、穿孔素和SLAMF 7表达进行定量。18名健康受试者作为对照。对治疗前后IgG 4-RD患者以及受累组织中的循环CD 4 + CTL进行了T细胞受体α和β链基因的下一代测序。与健康对照组相比，IgG 4-RD患者中循环CD 4 + TEM和TEMRA细胞未扩增。CD 4 + SLAMF 7 + TEM细胞（但不是TEMRA细胞）在IgG 4-RD患者中显著增加。在CD 4 + SLAMF 7 + TEM细胞中，IgG 4-RD患者的CD 8 α−细胞升高，但CD 8 α低细胞未升高。外周血中发现的CD 8 α− CD 4 + SLAMF 7 + TEM细胞的相同优势克隆也在受影响的组织中鉴定。CD 8 α−和CD 8 α低CD 4 + SLAMF 7 + TEM细胞均表达细胞溶解分子。糖皮质激素诱导的疾病缓解后，克隆扩增的CD 8 α−而非CD 8 α低CD 4 + SLAMF 7 + TEM细胞减少。CD 8 α− CD 4 + SLAMF 7+细胞毒性TEM细胞亚群在活动性IgG 4-RD患者中寡克隆扩增。该人群在糖皮质激素诱导的缓解后收缩。对该细胞群的进一步表征可以提供预后信息和治疗干预的靶点。
An unconventional population of CD4+SLAMF7+ cytotoxic TEM cells (CD4+CTLs) has been linked causally to IgG4-related disease (IgG4-RD). Glucocorticoids represent the first line therapeutic approach in patients with IgG4-RD but their mechanism of action in this specific condition remains unknown. Here we describe the impact of glucocorticoids on CD4+CTLs in IgG4-RD. CD8α, granzyme A, perforin, and SLAMF7 expression within the effector/memory compartment of CD45RO (TEM) and CD45RA (TEMRA) CD4+ T cells was quantified by flow cytometry in 18 active IgG4-RD patients at baseline and after 6 months of glucocorticoid treatment. Eighteen healthy subjects were studied as controls. Next-generation sequencing of the T-cell receptor α and β chain gene was performed on circulating CD4+CTLs in patients with IgG4-RD before and after treatment, and in affected tissues. Circulating CD4+ TEM and TEMRA cells were not expanded in IgG4-RD patients compared to healthy controls. CD4+SLAMF7+ TEM cells (but not TEMRA cells) were significantly increased among IgG4-RD patients. Within CD4+SLAMF7+ TEM cells, CD8α− but not CD8αlow cells were elevated in IgG4-RD patients. The same dominant clones of CD8α−CD4+SLAMF7+ TEM cells found in the peripheral blood were also identified in affected tissue. Both CD8α− and CD8αlow CD4+SLAMF7+ TEM cells expressed cytolytic molecules. Clonally expanded CD8α− but not CD8αlow CD4+SLAMF7+ TEM cells decreased following glucocorticoid-induced disease remission. A subset of CD8α−CD4+SLAMF7+ cytotoxic TEM cells is oligoclonally expanded in patients with active IgG4-RD. This population contracts following glucocorticoid-induced remission. Further characterization of this cell population may provide prognostic information and targets for therapeutic intervention.
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影响因子：
7.3
作者：
Oja AE;Vieira Braga FA;Remmerswaal EB;Kragten NA;Hertoghs KM;Zuo J;Moss PA;van Lier RA;van Gisbergen KP;Hombrink P
通讯作者：
Hombrink P
影响因子：
27.4
作者：
Wallace ZS;Mattoo H;Carruthers M;Mahajan VS;Della Torre E;Lee H;Kulikova M;Deshpande V;Pillai S;Stone JH
通讯作者：
Stone JH
慢性丙型肝炎和C中患者的血液和肝脏中不同的CD4+ CD8+双阳性T细胞。
影响因子：
3.7
作者：
Nascimbeni M;Pol S;Saunier B
通讯作者：
Saunier B
影响因子：
2.1
作者：
Campochiaro, C.;Ramirez, G. A.;Della-Torre, E.
通讯作者：
Della-Torre, E.
影响因子：
27.4
作者：
Della-Torre E;Feeney E;Deshpande V;Mattoo H;Mahajan V;Kulikova M;Wallace ZS;Carruthers M;Chung RT;Pillai S;Stone JH
通讯作者：
Stone JH