小柯机器人

英国伦敦大学学院Lucy S. K. Walker课题组发现，滤泡辅助性T细胞可预测1型糖尿病对共刺激阻断的反应。相关论文于2020年8月3日在线发表于国际学术期刊《自然—免疫学》。

据研究人员介绍，滤泡辅助性T（TFH）细胞与1型糖尿病（T1D）有关，并且其发育与CD28协同刺激有关。

研究人员测试了糖尿病小鼠模型和新发T1D患者中，使用CTLA-4-免疫球蛋白（Ig）融合蛋白（abatacept）的共刺激阻断作用下，TFH细胞是否减少。生物信息学分析表明，诱导型共刺激分子（ICOS）⁺TFH细胞和其他ICOS⁺群体，包括外周辅助T细胞，对共刺激阻断高度敏感。研究人员使用了TFH预处理数据来推导出一个模型，其可以预测T1D患者对abatacept的临床反应。使用两种独立的方法，研究人员证明了基线较高的ICOS⁺TFH细胞频率与abatacept给药后不良的临床反应有关。因此，TFH分析可能是一种新的分层工具，可以确定最有可能受益于共刺激阻断的患者。

附：英文原文

Title: Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes

Author: Natalie M. Edner, Frank Heuts, Niclas Thomas, Chun Jing Wang, Lina Petersone, Rupert Kenefeck, Alexandros Kogimtzis, Vitalijs Ovcinnikovs, Ellen M. Ross, Elisavet Ntavli, Yassin Elfaki, Martin Eichmann, Roman Baptista, Philip Ambery, Lutz Jermutus, Mark Peakman, Miranda Rosenthal, Lucy S. K. Walker

Issue&Volume: 2020-08-03

Abstract: Follicular helper T (TFH) cells are implicated in type 1 diabetes (T1D), and their development has been linked to CD28 costimulation. We tested whether TFH cells were decreased by costimulation blockade using the CTLA-4–immunoglobulin (Ig) fusion protein (abatacept) in a mouse model of diabetes and in individuals with new-onset T1D. Unbiased bioinformatics analysis identified that inducible costimulatory molecule (ICOS)+ TFH cells and other ICOS+ populations, including peripheral helper T cells, were highly sensitive to costimulation blockade. We used pretreatment TFH profiles to derive a model that could predict clinical response to abatacept in individuals with T1D. Using two independent approaches, we demonstrated that higher frequencies of ICOS+ TFH cells at baseline were associated with a poor clinical response following abatacept administration. Therefore, TFH analysis may represent a new stratification tool, permitting the identification of individuals most likely to benefit from costimulation blockade.

DOI: 10.1038/s41590-020-0744-z

Source: https://www.nature.com/articles/s41590-020-0744-z

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex