阿巴塔克普
封锁
免疫学
CD28
1型糖尿病
T细胞
医学
CXCR5型
自身免疫
生物
抗体
免疫系统
糖尿病
B细胞
内科学
内分泌学
受体
生发中心
美罗华
作者
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
出处
期刊:Nature Immunology
[Springer Nature]
日期:2020-08-03
卷期号:21 (10): 1244-1255
被引量:60
标识
DOI:10.1038/s41590-020-0744-z
摘要
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.
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