Open AccessFollicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes
Author(s) -
Natalie M. Edner,
Frank Heuts,
Niclas Thomas,
Chun Jing Wang,
Lina Petersone,
Rupert Kenefeck,
Alexandros Kogimtzis,
Vitalijs Ovcinnikovs,
Ellen M Ross,
Elisavet Ntavli,
Yassin Elfaki,
Martin Eichmann,
Roman Baptista,
Philip Ambery,
Lutz Jermutus,
Mark Peakman,
Miranda Rosenthal,
Lucy S. K. Walker
Publication year - 2020
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-020-0744-z
Subject(s) - abatacept , blockade , immunology , cd28 , type 1 diabetes , t cell , medicine , cxcr5 , autoimmunity , biology , antibody , immune system , diabetes mellitus , b cell , endocrinology , receptor , germinal center , rituximab
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.