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The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells
The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4(+) T cells that...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364140/ https://www.ncbi.nlm.nih.gov/pubmed/28392788 http://dx.doi.org/10.3389/fimmu.2017.00325 |
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author | Oja, Anna E. Vieira Braga, Felipe A. Remmerswaal, Ester B. M. Kragten, Natasja A. M. Hertoghs, Kirsten M. L. Zuo, Jianmin Moss, Paul A. van Lier, René A. W. van Gisbergen, Klaas P. J. M. Hombrink, Pleun |
author_facet | Oja, Anna E. Vieira Braga, Felipe A. Remmerswaal, Ester B. M. Kragten, Natasja A. M. Hertoghs, Kirsten M. L. Zuo, Jianmin Moss, Paul A. van Lier, René A. W. van Gisbergen, Klaas P. J. M. Hombrink, Pleun |
author_sort | Oja, Anna E. |
collection | PubMed |
description | The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4(+) T cells that conforms to the phenotype of cytotoxic CD8(+) T cells has received increased recognition. These cytotoxic CD4(+) T cells display constitutive expression of granzyme B and perforin at the protein level and mediate HLA class II-dependent killing of target cells. In humans, this cytotoxic profile is found within the human cytomegalovirus (hCMV)-specific, but not within the influenza- or Epstein–Barr virus-specific CD4(+) T cell populations, suggesting that, in particular, hCMV infection induces the formation of cytotoxic CD4(+) T cells. We have previously described that the transcription factor Homolog of Blimp-1 in T cells (Hobit) is specifically upregulated in CD45RA(+) effector CD8(+) T cells that arise after hCMV infection. Here, we describe the expression pattern of Hobit in human CD4(+) T cells. We found Hobit expression in cytotoxic CD4(+) T cells and accumulation of Hobit(+) CD4(+) T cells after primary hCMV infection. The Hobit(+) CD4(+) T cells displayed highly overlapping characteristics with Hobit(+) CD8(+) T cells, including the expression of cytotoxic molecules, T-bet, and CX3CR1. Interestingly, γδ(+) T cells that arise after hCMV infection also upregulate Hobit expression and display a similar effector phenotype as cytotoxic CD4(+) and CD8(+) T cells. These findings suggest a shared differentiation pathway in CD4(+), CD8(+), and γδ(+) T cells that may involve Hobit-driven acquisition of long-lived cytotoxic effector function. |
format | Online Article Text |
id | pubmed-5364140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53641402017-04-07 The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells Oja, Anna E. Vieira Braga, Felipe A. Remmerswaal, Ester B. M. Kragten, Natasja A. M. Hertoghs, Kirsten M. L. Zuo, Jianmin Moss, Paul A. van Lier, René A. W. van Gisbergen, Klaas P. J. M. Hombrink, Pleun Front Immunol Immunology The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4(+) T cells that conforms to the phenotype of cytotoxic CD8(+) T cells has received increased recognition. These cytotoxic CD4(+) T cells display constitutive expression of granzyme B and perforin at the protein level and mediate HLA class II-dependent killing of target cells. In humans, this cytotoxic profile is found within the human cytomegalovirus (hCMV)-specific, but not within the influenza- or Epstein–Barr virus-specific CD4(+) T cell populations, suggesting that, in particular, hCMV infection induces the formation of cytotoxic CD4(+) T cells. We have previously described that the transcription factor Homolog of Blimp-1 in T cells (Hobit) is specifically upregulated in CD45RA(+) effector CD8(+) T cells that arise after hCMV infection. Here, we describe the expression pattern of Hobit in human CD4(+) T cells. We found Hobit expression in cytotoxic CD4(+) T cells and accumulation of Hobit(+) CD4(+) T cells after primary hCMV infection. The Hobit(+) CD4(+) T cells displayed highly overlapping characteristics with Hobit(+) CD8(+) T cells, including the expression of cytotoxic molecules, T-bet, and CX3CR1. Interestingly, γδ(+) T cells that arise after hCMV infection also upregulate Hobit expression and display a similar effector phenotype as cytotoxic CD4(+) and CD8(+) T cells. These findings suggest a shared differentiation pathway in CD4(+), CD8(+), and γδ(+) T cells that may involve Hobit-driven acquisition of long-lived cytotoxic effector function. Frontiers Media S.A. 2017-03-24 /pmc/articles/PMC5364140/ /pubmed/28392788 http://dx.doi.org/10.3389/fimmu.2017.00325 Text en Copyright © 2017 Oja, Vieira Braga, Remmerswaal, Kragten, Hertoghs, Zuo, Moss, van Lier, van Gisbergen and Hombrink. 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) or licensor 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 Oja, Anna E. Vieira Braga, Felipe A. Remmerswaal, Ester B. M. Kragten, Natasja A. M. Hertoghs, Kirsten M. L. Zuo, Jianmin Moss, Paul A. van Lier, René A. W. van Gisbergen, Klaas P. J. M. Hombrink, Pleun The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells |
title | The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells |
title_full | The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells |
title_fullStr | The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells |
title_full_unstemmed | The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells |
title_short | The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells |
title_sort | transcription factor hobit identifies human cytotoxic cd4(+) t cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364140/ https://www.ncbi.nlm.nih.gov/pubmed/28392788 http://dx.doi.org/10.3389/fimmu.2017.00325 |
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