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

Research output: Contribution to journalArticle

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

Original languageEnglish
Pages (from-to)1244-1255
Number of pages12
JournalNature Immunology
Volume21
Issue number10
DOIs
Accepted/In press1 Jan 2020
Published1 Oct 2020

King's Authors

Abstract

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.

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