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

Follicular helper T cells (Tfh) are implicated in type 1 diabetes (T1D) and their development has been linked to CD28 costimulation. We tested whether Tfh were decreased by costimulation blockade using the CTLA-4-Ig fusion protein (Abatacept) in a mouse model of diabetes and in individuals with new onset T1D. Unbiased bioinformatic analysis identified that ICOS(+) Tfh, and other ICOS(+) populations including T-peripheral helper cells, were highly sensitive to costimulation blockade. We were able to use pre-treatment 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 at baseline were associated with a poor clinical response following Abatacept administration. Tfh analysis may therefore represent a new stratification tool, permitting the identification of individuals most likely to benefit from costimulation blockade.