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Variations in Cellular Responses of Mouse T Cells to Adenosine-5′-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage

A previous report has shown that regulatory T cells (Treg) were markedly more sensitive to adenosine-5′-triphosphate (ATP) than conventional T cells (Tconv). Another one has shown that Tregs and CD45RB(low) Tconvs, but not CD45RB(high) Tconvs, displayed similar high sensitivity to ATP. We have previ...

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Autores principales: Safya, Hanaa, Mellouk, Amine, Legrand, Julie, Le Gall, Sylvain M., Benbijja, Mohcine, Kanellopoulos-Langevin, Colette, Kanellopoulos, Jean M., Bobé, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835135/
https://www.ncbi.nlm.nih.gov/pubmed/29535730
http://dx.doi.org/10.3389/fimmu.2018.00360
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author Safya, Hanaa
Mellouk, Amine
Legrand, Julie
Le Gall, Sylvain M.
Benbijja, Mohcine
Kanellopoulos-Langevin, Colette
Kanellopoulos, Jean M.
Bobé, Pierre
author_facet Safya, Hanaa
Mellouk, Amine
Legrand, Julie
Le Gall, Sylvain M.
Benbijja, Mohcine
Kanellopoulos-Langevin, Colette
Kanellopoulos, Jean M.
Bobé, Pierre
author_sort Safya, Hanaa
collection PubMed
description A previous report has shown that regulatory T cells (Treg) were markedly more sensitive to adenosine-5′-triphosphate (ATP) than conventional T cells (Tconv). Another one has shown that Tregs and CD45RB(low) Tconvs, but not CD45RB(high) Tconvs, displayed similar high sensitivity to ATP. We have previously reported that CD45RB(low) Tconvs expressing B220/CD45RABC molecules in a pre-apoptotic stage are resistant to ATP stimulation due to the loss of P2X7 receptor (P2X7R) membrane expression. To gain a clearer picture on T-cell sensitivity to ATP, we have quantified four different cellular activities triggered by ATP in mouse T cells at different stages of activation/differentiation, in correlation with levels of P2X7R membrane expression. P2X7R expression significantly increases on Tconvs during differentiation from naive CD45RB(high)CD44(low) to effector/memory CD45RB(low)CD44(high) stage. Maximum levels of upregulation are reached on recently activated CD69(+) naive and memory Tconvs. Ectonucleotidases CD39 and CD73 expression levels increase in parallel with those of P2X7R. Recently activated CD69(+) CD45RB(high)CD44(low) Tconvs, although expressing high levels of P2X7R, fail to cleave homing receptor CD62L after ATP treatment, but efficiently form pores and externalize phosphatidylserine (PS). In contrast, naive CD45RB(high)CD44(low) Tconvs cleave CD62L with high efficiency although they express a lower level of P2X7, thus suggesting that P2X7R levels are not a limiting factor for signaling ATP-induced cellular responses. Contrary to common assumption, P2X7R-mediated cellular activities in mouse Tconvs are not triggered in an all-or-none manner, but depend on their stage of activation/differentiation. Compared to CD45RB(low) Tconvs, CD45RB(low)Foxp3(+) Tregs show significantly higher levels of P2X7R membrane expression and of sensitivity to ATP as evidenced by their high levels of CD62L shedding, pore formation and PS externalization observed after ATP treatment. In summary, the different abilities of ATP-treated Tconvs to form pore or cleave CD62L depending on their activation and differentiation state suggests that P2X7R signaling varies according to the physiological role of T convs during antigen activation in secondary lymphoid organs or trafficking to inflammatory sites.
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spelling pubmed-58351352018-03-13 Variations in Cellular Responses of Mouse T Cells to Adenosine-5′-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage Safya, Hanaa Mellouk, Amine Legrand, Julie Le Gall, Sylvain M. Benbijja, Mohcine Kanellopoulos-Langevin, Colette Kanellopoulos, Jean M. Bobé, Pierre Front Immunol Immunology A previous report has shown that regulatory T cells (Treg) were markedly more sensitive to adenosine-5′-triphosphate (ATP) than conventional T cells (Tconv). Another one has shown that Tregs and CD45RB(low) Tconvs, but not CD45RB(high) Tconvs, displayed similar high sensitivity to ATP. We have previously reported that CD45RB(low) Tconvs expressing B220/CD45RABC molecules in a pre-apoptotic stage are resistant to ATP stimulation due to the loss of P2X7 receptor (P2X7R) membrane expression. To gain a clearer picture on T-cell sensitivity to ATP, we have quantified four different cellular activities triggered by ATP in mouse T cells at different stages of activation/differentiation, in correlation with levels of P2X7R membrane expression. P2X7R expression significantly increases on Tconvs during differentiation from naive CD45RB(high)CD44(low) to effector/memory CD45RB(low)CD44(high) stage. Maximum levels of upregulation are reached on recently activated CD69(+) naive and memory Tconvs. Ectonucleotidases CD39 and CD73 expression levels increase in parallel with those of P2X7R. Recently activated CD69(+) CD45RB(high)CD44(low) Tconvs, although expressing high levels of P2X7R, fail to cleave homing receptor CD62L after ATP treatment, but efficiently form pores and externalize phosphatidylserine (PS). In contrast, naive CD45RB(high)CD44(low) Tconvs cleave CD62L with high efficiency although they express a lower level of P2X7, thus suggesting that P2X7R levels are not a limiting factor for signaling ATP-induced cellular responses. Contrary to common assumption, P2X7R-mediated cellular activities in mouse Tconvs are not triggered in an all-or-none manner, but depend on their stage of activation/differentiation. Compared to CD45RB(low) Tconvs, CD45RB(low)Foxp3(+) Tregs show significantly higher levels of P2X7R membrane expression and of sensitivity to ATP as evidenced by their high levels of CD62L shedding, pore formation and PS externalization observed after ATP treatment. In summary, the different abilities of ATP-treated Tconvs to form pore or cleave CD62L depending on their activation and differentiation state suggests that P2X7R signaling varies according to the physiological role of T convs during antigen activation in secondary lymphoid organs or trafficking to inflammatory sites. Frontiers Media S.A. 2018-02-27 /pmc/articles/PMC5835135/ /pubmed/29535730 http://dx.doi.org/10.3389/fimmu.2018.00360 Text en Copyright © 2018 Safya, Mellouk, Legrand, Le Gall, Benbijja, Kanellopoulos-Langevin, Kanellopoulos and Bobé. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Safya, Hanaa
Mellouk, Amine
Legrand, Julie
Le Gall, Sylvain M.
Benbijja, Mohcine
Kanellopoulos-Langevin, Colette
Kanellopoulos, Jean M.
Bobé, Pierre
Variations in Cellular Responses of Mouse T Cells to Adenosine-5′-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage
title Variations in Cellular Responses of Mouse T Cells to Adenosine-5′-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage
title_full Variations in Cellular Responses of Mouse T Cells to Adenosine-5′-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage
title_fullStr Variations in Cellular Responses of Mouse T Cells to Adenosine-5′-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage
title_full_unstemmed Variations in Cellular Responses of Mouse T Cells to Adenosine-5′-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage
title_short Variations in Cellular Responses of Mouse T Cells to Adenosine-5′-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage
title_sort variations in cellular responses of mouse t cells to adenosine-5′-triphosphate stimulation do not depend on p2x7 receptor expression levels but on their activation and differentiation stage
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835135/
https://www.ncbi.nlm.nih.gov/pubmed/29535730
http://dx.doi.org/10.3389/fimmu.2018.00360
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