Follicular helper T (T_FH) cells are implicated in type 1 diabetes (T1D), and their development has been linked to CD28 costimulation. We tested whether T_FH 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)⁺ T_FH cells and other ICOS⁺ populations, including peripheral helper T cells, were highly sensitive to costimulation blockade. We used pretreatment T_FH 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⁺ T_FH cells at baseline were associated with a poor clinical response following abatacept administration. Therefore, T_FH analysis may represent a new stratification tool, permitting the identification of individuals most likely to benefit from costimulation blockade.

滤泡辅助 T (T _FH ) 细胞与 1 型糖尿病 (T1D) 有关，其发育与 CD28 共刺激有关。我们在糖尿病小鼠模型和新发 T1D 个体中使用 CTLA-4-免疫球蛋白 (Ig) 融合蛋白（阿巴西普）测试了 T _FH细胞是否因共刺激阻断而减少。无偏见的生物信息学分析发现，诱导型共刺激分子 (ICOS) ⁺ T _FH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。我们使用治疗前 T _FH谱得出一个模型，可以预测 T1D 个体对阿巴西普的临床反应。使用两种独立的方法，我们证明基线时较高频率的 ICOS ⁺ T _FH细胞与阿巴西普给药后较差的临床反应相关。因此，T _FH分析可能代表一种新的分层工具，允许识别最有可能从共刺激封锁中受益的个体。