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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 and Reuter, Morgan A. , et al. (2018) In PLoS Pathogens 14(4).
Abstract

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... (More)

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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Contribution to journal
publication status
published
subject
in
PLoS Pathogens
volume
14
issue
4
article number
e1006973
publisher
Public Library of Science
external identifiers
  • pmid:29652923
  • scopus:85046491136
ISSN
1553-7374
DOI
10.1371/journal.ppat.1006973
language
English
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yes
id
2abd9d8e-ed34-4a1e-9ed2-5ffc03f0ec03
date added to LUP
2018-05-17 15:41:09
date last changed
2020-12-01 04:06:41
@article{2abd9d8e-ed34-4a1e-9ed2-5ffc03f0ec03,
  abstract     = {<p>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.</p>},
  author       = {Buggert, Marcus and Nguyen, Son and McLane, Laura M. and Steblyanko, Maria and Anikeeva, Nadia and Paquin-Proulx, Dominic and Del Rio Estrada, Perla M. and Ablanedo-Terrazas, Yuria and Noyan, Kajsa and Reuter, Morgan A. and Demers, Korey and Sandberg, Johan K. and Eller, Michael A. and Streeck, Hendrik and Jansson, Marianne and Nowak, Piotr and Sönnerborg, Anders and Canaday, David H. and Naji, Ali and Wherry, E. John and Robb, Merlin L. and Deeks, Steven G. and Reyes-Teran, Gustavo and Sykulev, Yuri and Karlsson, Annika C. and Betts, Michael R.},
  issn         = {1553-7374},
  language     = {eng},
  month        = {04},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1006973},
  doi          = {10.1371/journal.ppat.1006973},
  volume       = {14},
  year         = {2018},
}