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.
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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 |
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