CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis.
Atherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic pl...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-09-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008885 |
| _version_ | 1811339510599909376 |
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| author | Soumya Panigrahi Bonnie Chen Mike Fang Daria Potashnikova Alexey A Komissarov Anna Lebedeva Gillian M Michaelson Jonathan M Wyrick Stephen R Morris Scott F Sieg Mirko Paiardini Francois J Villinger Karem Harth Vikram S Kashyap Mark J Cameron Cheryl M Cameron Elena Vasilieva Leonid Margolis Souheil-Antoine Younes Nicholas T Funderburg David A Zidar Michael M Lederman Michael L Freeman |
| author_facet | Soumya Panigrahi Bonnie Chen Mike Fang Daria Potashnikova Alexey A Komissarov Anna Lebedeva Gillian M Michaelson Jonathan M Wyrick Stephen R Morris Scott F Sieg Mirko Paiardini Francois J Villinger Karem Harth Vikram S Kashyap Mark J Cameron Cheryl M Cameron Elena Vasilieva Leonid Margolis Souheil-Antoine Younes Nicholas T Funderburg David A Zidar Michael M Lederman Michael L Freeman |
| author_sort | Soumya Panigrahi |
| collection | DOAJ |
| description | Atherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic plaques and have been implicated in disease pathogenesis yet the mechanisms driving T cell recruitment to and activation within plaques are poorly defined. Here we investigated the role of CD8 T cells in atherosclerosis in a non-human primate model of HIV infection and in the HIV-uninfected elderly; we sought to identify factors that promote the activation, function, and recruitment to endothelium of CX3CR1+ CD8 T cells. We measured elevated expression of CX3CL1 and IL-15, and increased CD8 T cell numbers in the aortas of rhesus macaques infected with SIV or SHIV, and demonstrated similar findings in atherosclerotic vessels of HIV-uninfected humans. We found that recombinant TNF enhanced the production and release of CX3CL1 and bioactive IL-15 from aortic endothelial cells, but not from aortic smooth muscle cells. IL-15 in turn promoted CX3CR1 surface expression on and TNF synthesis by CD8 T cells, and IL-15-treated CD8 T cells exhibited enhanced CX3CL1-dependent chemoattraction toward endothelial cells in vitro. Finally, we show that CD8 T cells in human atherosclerotic plaques have an activated, resident phenotype consistent with in vivo IL-15 and CX3CL1 exposure. In this report, we define a novel model of CD8 T cell involvement in atherosclerosis whereby CX3CL1 and IL-15 operate in tandem within the vascular endothelium to promote infiltration by activated CX3CR1+ memory CD8 T cells that drive further endothelial activation via TNF. We propose that these interactions are prevalent in aging and in PLWH, populations where circulating activated CX3CR1+ CD8 T cell numbers are often expanded. |
| first_indexed | 2024-04-13T18:27:42Z |
| format | Article |
| id | doaj.art-ac62c44d1e6c4fe69f1c451e39acc988 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-13T18:27:42Z |
| publishDate | 2020-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-ac62c44d1e6c4fe69f1c451e39acc9882022-12-22T02:35:12ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-09-01169e100888510.1371/journal.ppat.1008885CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis.Soumya PanigrahiBonnie ChenMike FangDaria PotashnikovaAlexey A KomissarovAnna LebedevaGillian M MichaelsonJonathan M WyrickStephen R MorrisScott F SiegMirko PaiardiniFrancois J VillingerKarem HarthVikram S KashyapMark J CameronCheryl M CameronElena VasilievaLeonid MargolisSouheil-Antoine YounesNicholas T FunderburgDavid A ZidarMichael M LedermanMichael L FreemanAtherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic plaques and have been implicated in disease pathogenesis yet the mechanisms driving T cell recruitment to and activation within plaques are poorly defined. Here we investigated the role of CD8 T cells in atherosclerosis in a non-human primate model of HIV infection and in the HIV-uninfected elderly; we sought to identify factors that promote the activation, function, and recruitment to endothelium of CX3CR1+ CD8 T cells. We measured elevated expression of CX3CL1 and IL-15, and increased CD8 T cell numbers in the aortas of rhesus macaques infected with SIV or SHIV, and demonstrated similar findings in atherosclerotic vessels of HIV-uninfected humans. We found that recombinant TNF enhanced the production and release of CX3CL1 and bioactive IL-15 from aortic endothelial cells, but not from aortic smooth muscle cells. IL-15 in turn promoted CX3CR1 surface expression on and TNF synthesis by CD8 T cells, and IL-15-treated CD8 T cells exhibited enhanced CX3CL1-dependent chemoattraction toward endothelial cells in vitro. Finally, we show that CD8 T cells in human atherosclerotic plaques have an activated, resident phenotype consistent with in vivo IL-15 and CX3CL1 exposure. In this report, we define a novel model of CD8 T cell involvement in atherosclerosis whereby CX3CL1 and IL-15 operate in tandem within the vascular endothelium to promote infiltration by activated CX3CR1+ memory CD8 T cells that drive further endothelial activation via TNF. We propose that these interactions are prevalent in aging and in PLWH, populations where circulating activated CX3CR1+ CD8 T cell numbers are often expanded.https://doi.org/10.1371/journal.ppat.1008885 |
| spellingShingle | Soumya Panigrahi Bonnie Chen Mike Fang Daria Potashnikova Alexey A Komissarov Anna Lebedeva Gillian M Michaelson Jonathan M Wyrick Stephen R Morris Scott F Sieg Mirko Paiardini Francois J Villinger Karem Harth Vikram S Kashyap Mark J Cameron Cheryl M Cameron Elena Vasilieva Leonid Margolis Souheil-Antoine Younes Nicholas T Funderburg David A Zidar Michael M Lederman Michael L Freeman CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis. PLoS Pathogens |
| title | CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis. |
| title_full | CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis. |
| title_fullStr | CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis. |
| title_full_unstemmed | CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis. |
| title_short | CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis. |
| title_sort | cx3cl1 and il 15 promote cd8 t cell chemoattraction in hiv and in atherosclerosis |
| url | https://doi.org/10.1371/journal.ppat.1008885 |
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