UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Edner, NM; Heuts, F; Thomas, N; Wang, CJ; Petersone, L; Kenefeck, R; Kogimtzis, A; ... Walker, LSK; + view all (2020) Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes. Nature Immunology , 21 pp. 1244-1255. 10.1038/s41590-020-0744-z. Green open access

[thumbnail of Edner et al Manuscript to Deposit.pdf]
Preview
Text
Edner et al Manuscript to Deposit.pdf - Accepted Version

Download (11MB) | Preview

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.

Type: Article
Title: Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41590-020-0744-z
Publisher version: https://doi.org/10.1038/s41590-020-0744-z
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Follicular T-helper cells, Immunosuppression, Type 1 diabetes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10108608
Downloads since deposit
100Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item