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

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