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

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. The CTLA-4-Ig fusion protein (abatacept) can have beneficial effects in autoimmune disease. Walker and colleagues show in mouse and human type 1 diabetes that abatacept targets pathogenic follicular helper T cells, and the frequencies of these cells at baseline can be used to stratify treatment responses in patients.