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Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease

CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine produc...

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Autores principales: Buggert, Marcus, Nguyen, Son, McLane, Laura M., Steblyanko, Maria, Anikeeva, Nadia, Paquin-Proulx, Dominic, Del Rio Estrada, Perla M., Ablanedo-Terrazas, Yuria, Noyan, Kajsa, Reuter, Morgan A., Demers, Korey, Sandberg, Johan K., Eller, Michael A., Streeck, Hendrik, Jansson, Marianne, Nowak, Piotr, Sönnerborg, Anders, Canaday, David H., Naji, Ali, Wherry, E. John, Robb, Merlin L., Deeks, Steven G., Reyes-Teran, Gustavo, Sykulev, Yuri, Karlsson, Annika C., Betts, Michael R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919077/
https://www.ncbi.nlm.nih.gov/pubmed/29652923
http://dx.doi.org/10.1371/journal.ppat.1006973
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author Buggert, Marcus
Nguyen, Son
McLane, Laura M.
Steblyanko, Maria
Anikeeva, Nadia
Paquin-Proulx, Dominic
Del Rio Estrada, Perla M.
Ablanedo-Terrazas, Yuria
Noyan, Kajsa
Reuter, Morgan A.
Demers, Korey
Sandberg, Johan K.
Eller, Michael A.
Streeck, Hendrik
Jansson, Marianne
Nowak, Piotr
Sönnerborg, Anders
Canaday, David H.
Naji, Ali
Wherry, E. John
Robb, Merlin L.
Deeks, Steven G.
Reyes-Teran, Gustavo
Sykulev, Yuri
Karlsson, Annika C.
Betts, Michael R.
author_facet Buggert, Marcus
Nguyen, Son
McLane, Laura M.
Steblyanko, Maria
Anikeeva, Nadia
Paquin-Proulx, Dominic
Del Rio Estrada, Perla M.
Ablanedo-Terrazas, Yuria
Noyan, Kajsa
Reuter, Morgan A.
Demers, Korey
Sandberg, Johan K.
Eller, Michael A.
Streeck, Hendrik
Jansson, Marianne
Nowak, Piotr
Sönnerborg, Anders
Canaday, David H.
Naji, Ali
Wherry, E. John
Robb, Merlin L.
Deeks, Steven G.
Reyes-Teran, Gustavo
Sykulev, Yuri
Karlsson, Annika C.
Betts, Michael R.
author_sort Buggert, Marcus
collection PubMed
description CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.
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spelling pubmed-59190772018-05-06 Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease Buggert, Marcus Nguyen, Son McLane, Laura M. Steblyanko, Maria Anikeeva, Nadia Paquin-Proulx, Dominic Del Rio Estrada, Perla M. Ablanedo-Terrazas, Yuria Noyan, Kajsa Reuter, Morgan A. Demers, Korey Sandberg, Johan K. Eller, Michael A. Streeck, Hendrik Jansson, Marianne Nowak, Piotr Sönnerborg, Anders Canaday, David H. Naji, Ali Wherry, E. John Robb, Merlin L. Deeks, Steven G. Reyes-Teran, Gustavo Sykulev, Yuri Karlsson, Annika C. Betts, Michael R. PLoS Pathog Research Article CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues. Public Library of Science 2018-04-13 /pmc/articles/PMC5919077/ /pubmed/29652923 http://dx.doi.org/10.1371/journal.ppat.1006973 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Buggert, Marcus
Nguyen, Son
McLane, Laura M.
Steblyanko, Maria
Anikeeva, Nadia
Paquin-Proulx, Dominic
Del Rio Estrada, Perla M.
Ablanedo-Terrazas, Yuria
Noyan, Kajsa
Reuter, Morgan A.
Demers, Korey
Sandberg, Johan K.
Eller, Michael A.
Streeck, Hendrik
Jansson, Marianne
Nowak, Piotr
Sönnerborg, Anders
Canaday, David H.
Naji, Ali
Wherry, E. John
Robb, Merlin L.
Deeks, Steven G.
Reyes-Teran, Gustavo
Sykulev, Yuri
Karlsson, Annika C.
Betts, Michael R.
Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
title Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
title_full Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
title_fullStr Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
title_full_unstemmed Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
title_short Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
title_sort limited immune surveillance in lymphoid tissue by cytolytic cd4+ t cells during health and hiv disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919077/
https://www.ncbi.nlm.nih.gov/pubmed/29652923
http://dx.doi.org/10.1371/journal.ppat.1006973
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