Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes.
Natalie Mona EdnerFrank HeutsNiclas ThomasChun Jing WangLina PetersoneRupert KenefeckAlexandros KogimtzisVitalijs OvcinnikovsEllen M RossElisavet NtavliYassin ElfakiMartin EichmannRoman BaptistaPhilip AmberyLutz JermutusMark PeakmanMiranda RosenthalLucy Sarah Kate WalkerPublished in: Nature immunology (2020)
Follicular helper T (TFH) cells are implicated in type 1 diabetes (T1D), and their development has been linked to CD28 costimulation. We tested whether TFH 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)+ TFH cells and other ICOS+ populations, including peripheral helper T cells, were highly sensitive to costimulation blockade. We used pretreatment 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 cells at baseline were associated with a poor clinical response following abatacept administration. Therefore, TFH analysis may represent a new stratification tool, permitting the identification of individuals most likely to benefit from costimulation blockade.
Keyphrases
- type diabetes
- induced apoptosis
- cell cycle arrest
- rheumatoid arthritis
- mouse model
- glycemic control
- regulatory t cells
- dendritic cells
- endoplasmic reticulum stress
- signaling pathway
- cell death
- oxidative stress
- rheumatoid arthritis patients
- systemic lupus erythematosus
- cell proliferation
- disease activity
- high resolution
- metabolic syndrome