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

Abstract

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.