A rapid diagnostic test for human regulatory T-cell function to enable regulatory T-cell therapy

James B. Canavan; Behdad Afzali; Cristiano Scotta; Henrieta Fazekasova; Francis C. Edozie; Thomas T. Macdonald; Maria P. Hernandez-Fuentes; Giovanna Lombardi; Graham M. Lord

doi:10.1182/blood-2011-09-380048

A rapid diagnostic test for human regulatory T-cell function to enable regulatory T-cell therapy

James B. Canavan, Behdad Afzali, Cristiano Scotta, Henrieta Fazekasova, Francis C. Edozie, Thomas T. Macdonald, Maria P. Hernandez-Fuentes, Giovanna Lombardi, Graham M. Lord

Research output: Contribution to journal › Article › peer-review

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Abstract

Regulatory T cells (CD4(+)CD25(hi)CD127(lo)FOXP3(+) T cells [Tregs]) are a population of lymphocytes involved in the maintenance of self-tolerance. Abnormalities in function or number of Tregs are a feature of autoimmune diseases in humans. The ability to expand functional Tregs ex vivo makes them ideal candidates for autologous cell therapy to treat human autoimmune diseases and to induce tolerance to transplants. Current tests of Treg function typically take up to 120 hours, a kinetic disadvantage as clinical trials of Tregs will be critically dependent on the availability of rapid diagnostic tests before infusion into humans. Here we evaluate a 7-hour flow cytometric assay for assessing Treg function, using suppression of the activation markers CD69 and CD154 on responder T cells (CD4(+)CD25(-) [Tresp]), compared with traditional assays involving inhibition of CFSE dilution and cytokine production. In both freshly isolated and ex vivo expanded Tregs, we describe excellent correlation with gold standard suppressor cell assays. We propose that the kinetic advantage of the new assay may place it as the preferred rapid diagnostic test for the evaluation of Treg function in forthcoming clinical trials of cell therapy, enabling the translation of the large body of preclinical data into potentially useful treatments for human diseases.

Original language	English
Pages (from-to)	e57-e66
Number of pages	10
Journal	Blood
Volume	119
Issue number	8
DOIs	https://doi.org/10.1182/blood-2011-09-380048
Publication status	Published - 23 Feb 2012

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title = "A rapid diagnostic test for human regulatory T-cell function to enable regulatory T-cell therapy",

abstract = "Regulatory T cells (CD4(+)CD25(hi)CD127(lo)FOXP3(+) T cells [Tregs]) are a population of lymphocytes involved in the maintenance of self-tolerance. Abnormalities in function or number of Tregs are a feature of autoimmune diseases in humans. The ability to expand functional Tregs ex vivo makes them ideal candidates for autologous cell therapy to treat human autoimmune diseases and to induce tolerance to transplants. Current tests of Treg function typically take up to 120 hours, a kinetic disadvantage as clinical trials of Tregs will be critically dependent on the availability of rapid diagnostic tests before infusion into humans. Here we evaluate a 7-hour flow cytometric assay for assessing Treg function, using suppression of the activation markers CD69 and CD154 on responder T cells (CD4(+)CD25(-) [Tresp]), compared with traditional assays involving inhibition of CFSE dilution and cytokine production. In both freshly isolated and ex vivo expanded Tregs, we describe excellent correlation with gold standard suppressor cell assays. We propose that the kinetic advantage of the new assay may place it as the preferred rapid diagnostic test for the evaluation of Treg function in forthcoming clinical trials of cell therapy, enabling the translation of the large body of preclinical data into potentially useful treatments for human diseases.",

author = "Canavan, {James B.} and Behdad Afzali and Cristiano Scotta and Henrieta Fazekasova and Edozie, {Francis C.} and Macdonald, {Thomas T.} and Hernandez-Fuentes, {Maria P.} and Giovanna Lombardi and Lord, {Graham M.}",

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AU - Canavan, James B.

AU - Afzali, Behdad

AU - Scotta, Cristiano

AU - Fazekasova, Henrieta

AU - Edozie, Francis C.

AU - Macdonald, Thomas T.

AU - Hernandez-Fuentes, Maria P.

AU - Lombardi, Giovanna

AU - Lord, Graham M.

PY - 2012/2/23

Y1 - 2012/2/23

N2 - Regulatory T cells (CD4(+)CD25(hi)CD127(lo)FOXP3(+) T cells [Tregs]) are a population of lymphocytes involved in the maintenance of self-tolerance. Abnormalities in function or number of Tregs are a feature of autoimmune diseases in humans. The ability to expand functional Tregs ex vivo makes them ideal candidates for autologous cell therapy to treat human autoimmune diseases and to induce tolerance to transplants. Current tests of Treg function typically take up to 120 hours, a kinetic disadvantage as clinical trials of Tregs will be critically dependent on the availability of rapid diagnostic tests before infusion into humans. Here we evaluate a 7-hour flow cytometric assay for assessing Treg function, using suppression of the activation markers CD69 and CD154 on responder T cells (CD4(+)CD25(-) [Tresp]), compared with traditional assays involving inhibition of CFSE dilution and cytokine production. In both freshly isolated and ex vivo expanded Tregs, we describe excellent correlation with gold standard suppressor cell assays. We propose that the kinetic advantage of the new assay may place it as the preferred rapid diagnostic test for the evaluation of Treg function in forthcoming clinical trials of cell therapy, enabling the translation of the large body of preclinical data into potentially useful treatments for human diseases.

AB - Regulatory T cells (CD4(+)CD25(hi)CD127(lo)FOXP3(+) T cells [Tregs]) are a population of lymphocytes involved in the maintenance of self-tolerance. Abnormalities in function or number of Tregs are a feature of autoimmune diseases in humans. The ability to expand functional Tregs ex vivo makes them ideal candidates for autologous cell therapy to treat human autoimmune diseases and to induce tolerance to transplants. Current tests of Treg function typically take up to 120 hours, a kinetic disadvantage as clinical trials of Tregs will be critically dependent on the availability of rapid diagnostic tests before infusion into humans. Here we evaluate a 7-hour flow cytometric assay for assessing Treg function, using suppression of the activation markers CD69 and CD154 on responder T cells (CD4(+)CD25(-) [Tresp]), compared with traditional assays involving inhibition of CFSE dilution and cytokine production. In both freshly isolated and ex vivo expanded Tregs, we describe excellent correlation with gold standard suppressor cell assays. We propose that the kinetic advantage of the new assay may place it as the preferred rapid diagnostic test for the evaluation of Treg function in forthcoming clinical trials of cell therapy, enabling the translation of the large body of preclinical data into potentially useful treatments for human diseases.

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DO - 10.1182/blood-2011-09-380048

M3 - Article

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SN - 1528-0020

VL - 119

SP - e57-e66

JO - Blood

JF - Blood

IS - 8

ER -

A rapid diagnostic test for human regulatory T-cell function to enable regulatory T-cell therapy

Abstract

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