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TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells

T cell activation is initiated upon ligand engagement of the T cell receptor (TCR) and costimulatory receptors. The CD28 molecule acts as a major costimulatory receptor in promoting full activation of naive T cells. However, despite extensive studies, why naive T cell activation requires concurrent...

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Autores principales: Xia, Fan, Qian, Cheng-Rui, Xun, Zhou, Hamon, Yannick, Sartre, Anne-Marie, Formisano, Anthony, Mailfert, Sébastien, Phelipot, Marie-Claire, Billaudeau, Cyrille, Jaeger, Sébastien, Nunès, Jacques A., Guo, Xiao-Jun, He, Hai-Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288997/
https://www.ncbi.nlm.nih.gov/pubmed/30564247
http://dx.doi.org/10.3389/fimmu.2018.02864
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author Xia, Fan
Qian, Cheng-Rui
Xun, Zhou
Hamon, Yannick
Sartre, Anne-Marie
Formisano, Anthony
Mailfert, Sébastien
Phelipot, Marie-Claire
Billaudeau, Cyrille
Jaeger, Sébastien
Nunès, Jacques A.
Guo, Xiao-Jun
He, Hai-Tao
author_facet Xia, Fan
Qian, Cheng-Rui
Xun, Zhou
Hamon, Yannick
Sartre, Anne-Marie
Formisano, Anthony
Mailfert, Sébastien
Phelipot, Marie-Claire
Billaudeau, Cyrille
Jaeger, Sébastien
Nunès, Jacques A.
Guo, Xiao-Jun
He, Hai-Tao
author_sort Xia, Fan
collection PubMed
description T cell activation is initiated upon ligand engagement of the T cell receptor (TCR) and costimulatory receptors. The CD28 molecule acts as a major costimulatory receptor in promoting full activation of naive T cells. However, despite extensive studies, why naive T cell activation requires concurrent stimulation of both the TCR and costimulatory receptors remains poorly understood. Here, we explore this issue by analyzing calcium response as a key early signaling event to elicit T cell activation. Experiments using mouse naive CD4(+) T cells showed that engagement of the TCR or CD28 with the respective cognate ligand was able to trigger a rise in fluctuating calcium mobilization levels, as shown by the frequency and average response magnitude of the reacting cells compared with basal levels occurred in unstimulated cells. The engagement of both TCR and CD28 enabled a further increase of these two metrics. However, such increases did not sufficiently explain the importance of the CD28 pathways to the functionally relevant calcium responses in T cell activation. Through the autocorrelation analysis of calcium time series data, we found that combined but not separate TCR and CD28 stimulation significantly prolonged the average decay time (τ) of the calcium signal amplitudes determined with the autocorrelation function, compared with its value in unstimulated cells. This increasement of decay time (τ) uniquely characterizes the fluctuating calcium response triggered by concurrent stimulation of TCR and CD28, as it could not be achieved with either stronger TCR stimuli or by co-engaging both TCR and LFA-1, and likely represents an important feature of competent early signaling to provoke efficient T cell activation. Our work has thus provided new insights into the interplay between the TCR and CD28 early signaling pathways critical to trigger naive T cell activation.
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spelling pubmed-62889972018-12-18 TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells Xia, Fan Qian, Cheng-Rui Xun, Zhou Hamon, Yannick Sartre, Anne-Marie Formisano, Anthony Mailfert, Sébastien Phelipot, Marie-Claire Billaudeau, Cyrille Jaeger, Sébastien Nunès, Jacques A. Guo, Xiao-Jun He, Hai-Tao Front Immunol Immunology T cell activation is initiated upon ligand engagement of the T cell receptor (TCR) and costimulatory receptors. The CD28 molecule acts as a major costimulatory receptor in promoting full activation of naive T cells. However, despite extensive studies, why naive T cell activation requires concurrent stimulation of both the TCR and costimulatory receptors remains poorly understood. Here, we explore this issue by analyzing calcium response as a key early signaling event to elicit T cell activation. Experiments using mouse naive CD4(+) T cells showed that engagement of the TCR or CD28 with the respective cognate ligand was able to trigger a rise in fluctuating calcium mobilization levels, as shown by the frequency and average response magnitude of the reacting cells compared with basal levels occurred in unstimulated cells. The engagement of both TCR and CD28 enabled a further increase of these two metrics. However, such increases did not sufficiently explain the importance of the CD28 pathways to the functionally relevant calcium responses in T cell activation. Through the autocorrelation analysis of calcium time series data, we found that combined but not separate TCR and CD28 stimulation significantly prolonged the average decay time (τ) of the calcium signal amplitudes determined with the autocorrelation function, compared with its value in unstimulated cells. This increasement of decay time (τ) uniquely characterizes the fluctuating calcium response triggered by concurrent stimulation of TCR and CD28, as it could not be achieved with either stronger TCR stimuli or by co-engaging both TCR and LFA-1, and likely represents an important feature of competent early signaling to provoke efficient T cell activation. Our work has thus provided new insights into the interplay between the TCR and CD28 early signaling pathways critical to trigger naive T cell activation. Frontiers Media S.A. 2018-12-04 /pmc/articles/PMC6288997/ /pubmed/30564247 http://dx.doi.org/10.3389/fimmu.2018.02864 Text en Copyright © 2018 Xia, Qian, Xun, Hamon, Sartre, Formisano, Mailfert, Phelipot, Billaudeau, Jaeger, Nunès, Guo and He. 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(s) 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
Xia, Fan
Qian, Cheng-Rui
Xun, Zhou
Hamon, Yannick
Sartre, Anne-Marie
Formisano, Anthony
Mailfert, Sébastien
Phelipot, Marie-Claire
Billaudeau, Cyrille
Jaeger, Sébastien
Nunès, Jacques A.
Guo, Xiao-Jun
He, Hai-Tao
TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells
title TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells
title_full TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells
title_fullStr TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells
title_full_unstemmed TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells
title_short TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells
title_sort tcr and cd28 concomitant stimulation elicits a distinctive calcium response in naive t cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288997/
https://www.ncbi.nlm.nih.gov/pubmed/30564247
http://dx.doi.org/10.3389/fimmu.2018.02864
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