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Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection
CD8(+) T cells play an important role in host resistance to many viral infections, but the underlying transcriptional mechanisms governing their differentiation and functionality remain poorly defined. By using a highly virulent systemic and respiratory poxvirus infection in mice, we show that the t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061747/ https://www.ncbi.nlm.nih.gov/pubmed/27790219 http://dx.doi.org/10.3389/fimmu.2016.00425 |
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author | Abboud, Georges Stanfield, Jessica Tahiliani, Vikas Desai, Pritesh Hutchinson, Tarun E. Lorentsen, Kyle J. Cho, Jonathan J. Avram, Dorina Salek-Ardakani, Shahram |
author_facet | Abboud, Georges Stanfield, Jessica Tahiliani, Vikas Desai, Pritesh Hutchinson, Tarun E. Lorentsen, Kyle J. Cho, Jonathan J. Avram, Dorina Salek-Ardakani, Shahram |
author_sort | Abboud, Georges |
collection | PubMed |
description | CD8(+) T cells play an important role in host resistance to many viral infections, but the underlying transcriptional mechanisms governing their differentiation and functionality remain poorly defined. By using a highly virulent systemic and respiratory poxvirus infection in mice, we show that the transcription factor Bcl11b provides a dual trigger that sustains the clonal expansion of virus-specific effector CD8(+) T cells, while simultaneously suppressing the expression of surface markers associated with short-lived effector cell (SLEC) differentiation. Additionally, we demonstrate that Bcl11b supports the acquisition of memory precursor effector cell (MPEC) phenotype and, thus, its absence causes near complete loss of lymphoid and lung-resident memory cells. Interestingly, despite having normal levels of T-bet and Eomesodermin, Bcl11b-deficient CD8(+) T cells failed to execute effector differentiation needed for anti-viral cytokine production and degranulation, suggesting a non-redundant role of Bcl11b in regulation of this program. Thus, Bcl11b is a critical player in fate decision of SLECs and MPECs, as well as effector function and memory formation. |
format | Online Article Text |
id | pubmed-5061747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50617472016-10-27 Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection Abboud, Georges Stanfield, Jessica Tahiliani, Vikas Desai, Pritesh Hutchinson, Tarun E. Lorentsen, Kyle J. Cho, Jonathan J. Avram, Dorina Salek-Ardakani, Shahram Front Immunol Immunology CD8(+) T cells play an important role in host resistance to many viral infections, but the underlying transcriptional mechanisms governing their differentiation and functionality remain poorly defined. By using a highly virulent systemic and respiratory poxvirus infection in mice, we show that the transcription factor Bcl11b provides a dual trigger that sustains the clonal expansion of virus-specific effector CD8(+) T cells, while simultaneously suppressing the expression of surface markers associated with short-lived effector cell (SLEC) differentiation. Additionally, we demonstrate that Bcl11b supports the acquisition of memory precursor effector cell (MPEC) phenotype and, thus, its absence causes near complete loss of lymphoid and lung-resident memory cells. Interestingly, despite having normal levels of T-bet and Eomesodermin, Bcl11b-deficient CD8(+) T cells failed to execute effector differentiation needed for anti-viral cytokine production and degranulation, suggesting a non-redundant role of Bcl11b in regulation of this program. Thus, Bcl11b is a critical player in fate decision of SLECs and MPECs, as well as effector function and memory formation. Frontiers Media S.A. 2016-10-13 /pmc/articles/PMC5061747/ /pubmed/27790219 http://dx.doi.org/10.3389/fimmu.2016.00425 Text en Copyright © 2016 Abboud, Stanfield, Tahiliani, Desai, Hutchinson, Lorentsen, Cho, Avram and Salek-Ardakani. 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 Abboud, Georges Stanfield, Jessica Tahiliani, Vikas Desai, Pritesh Hutchinson, Tarun E. Lorentsen, Kyle J. Cho, Jonathan J. Avram, Dorina Salek-Ardakani, Shahram Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection |
title | Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection |
title_full | Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection |
title_fullStr | Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection |
title_full_unstemmed | Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection |
title_short | Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection |
title_sort | transcription factor bcl11b controls effector and memory cd8 t cell fate decision and function during poxvirus infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061747/ https://www.ncbi.nlm.nih.gov/pubmed/27790219 http://dx.doi.org/10.3389/fimmu.2016.00425 |
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