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Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients

BACKGROUND: CD28(neg) T cells, which display functional characteristic of oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be pathologically relevant in rheumatoid arthritis manifestation. The CD28 co-stimulation blockade by abatacept can prevent the generation of CD28(neg) T-c...

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Autores principales: Imberti, Luisa, Scarsi, Mirko, Zanotti, Cinzia, Chiarini, Marco, Bertoli, Diego, Tincani, Angela, Airò, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310138/
https://www.ncbi.nlm.nih.gov/pubmed/25592982
http://dx.doi.org/10.1186/s12967-014-0363-2
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author Imberti, Luisa
Scarsi, Mirko
Zanotti, Cinzia
Chiarini, Marco
Bertoli, Diego
Tincani, Angela
Airò, Paolo
author_facet Imberti, Luisa
Scarsi, Mirko
Zanotti, Cinzia
Chiarini, Marco
Bertoli, Diego
Tincani, Angela
Airò, Paolo
author_sort Imberti, Luisa
collection PubMed
description BACKGROUND: CD28(neg) T cells, which display functional characteristic of oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be pathologically relevant in rheumatoid arthritis manifestation. The CD28 co-stimulation blockade by abatacept can prevent the generation of CD28(neg) T-cell populations in these patients. METHODS: Samples were obtained before and after 12 months of abatacept therapy. T-cell phenotype and T-cell receptor diversity were evaluated by flow cytometry and complementarity-determining region-3 spectratyping, respectively, while telomerase reverse-transcriptase gene level was measured by real-time PCR. RESULTS: Abatacept induces a decrease of the percentage and number of CD4(+)CD28(neg) T cells and a reduction of T-cell repertoire restrictions; these features are directly correlated. Thymic output and telomerase activity are not modified by the therapy. CONCLUSIONS: Abatacept-induced decrease of peripheral T-cell repertoire restrictions can due to a reduced generation of senescent, chronically stimulated CD4(+)CD28(neg) T cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0363-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-43101382015-01-30 Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients Imberti, Luisa Scarsi, Mirko Zanotti, Cinzia Chiarini, Marco Bertoli, Diego Tincani, Angela Airò, Paolo J Transl Med Research BACKGROUND: CD28(neg) T cells, which display functional characteristic of oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be pathologically relevant in rheumatoid arthritis manifestation. The CD28 co-stimulation blockade by abatacept can prevent the generation of CD28(neg) T-cell populations in these patients. METHODS: Samples were obtained before and after 12 months of abatacept therapy. T-cell phenotype and T-cell receptor diversity were evaluated by flow cytometry and complementarity-determining region-3 spectratyping, respectively, while telomerase reverse-transcriptase gene level was measured by real-time PCR. RESULTS: Abatacept induces a decrease of the percentage and number of CD4(+)CD28(neg) T cells and a reduction of T-cell repertoire restrictions; these features are directly correlated. Thymic output and telomerase activity are not modified by the therapy. CONCLUSIONS: Abatacept-induced decrease of peripheral T-cell repertoire restrictions can due to a reduced generation of senescent, chronically stimulated CD4(+)CD28(neg) T cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0363-2) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-16 /pmc/articles/PMC4310138/ /pubmed/25592982 http://dx.doi.org/10.1186/s12967-014-0363-2 Text en © Imberti et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Imberti, Luisa
Scarsi, Mirko
Zanotti, Cinzia
Chiarini, Marco
Bertoli, Diego
Tincani, Angela
Airò, Paolo
Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients
title Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients
title_full Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients
title_fullStr Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients
title_full_unstemmed Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients
title_short Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients
title_sort reduced t-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310138/
https://www.ncbi.nlm.nih.gov/pubmed/25592982
http://dx.doi.org/10.1186/s12967-014-0363-2
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