CCR5 expression levels influence NFAT translocation, IL-2 production, and subsequent signaling events during T lymphocyte activation
Ligands of CCR5, the major coreceptor of HIV-1, costimulate T lymphocyte activation. However, the full impact of CCR5 expression on T cell responses remains unknown. Here, we show that compared with CCR5(+/+), T cells from CCR5(-/-) mice secrete lower amounts of IL-2, and a similar phenotype is observed in humans who lack CCR5 expression (CCR5-Delta32/Delta32 homozygotes) as well as after Ab-mediated blockade of CCR5 in human T cells genetically intact for CCR5 expression. Conversely, overexpression of CCR5 in human T cells results in enhanced IL-2 production. CCR5 surface levels correlate positively with IL-2 protein and mRNA abundance, suggesting that CCR5 affects IL-2 gene regulation. Signaling via CCR5 resulted in NFAT transactivation in T cells that was blocked by Abs against CCR5 agonists, suggesting a link between CCR5 and downstream pathways that influence IL-2 expression. Furthermore, murine T cells lacking CCR5 had reduced levels of intranuclear NFAT following activation. Accordingly, CCR5 expression also promoted IL-2-dependent events, including CD25 expression, STAT5 phosphorylation, and T cell proliferation. We therefore suggest that by influencing a NFAT-mediated pathway that regulates IL-2 production and IL-2-dependent events, CCR5 may play a critical role in T cell responses. In accord with our prior inferences from genetic-epidemiologic studies, such CCR5-dependent responses might constitute a viral entry-independent mechanism by which CCR5 may influence HIV-AIDS pathogenesis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:182 |
|---|---|
| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 182(2009), 1 vom: 01. Jan., Seite 171-82 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Camargo, Jose F [VerfasserIn] |
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| Anmerkungen: |
Date Completed 13.02.2009 Date Revised 20.10.2021 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM185422918 |
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| 100 | 1 | |a Camargo, Jose F |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CCR5 expression levels influence NFAT translocation, IL-2 production, and subsequent signaling events during T lymphocyte activation |
| 264 | 1 | |c 2009 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 13.02.2009 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Ligands of CCR5, the major coreceptor of HIV-1, costimulate T lymphocyte activation. However, the full impact of CCR5 expression on T cell responses remains unknown. Here, we show that compared with CCR5(+/+), T cells from CCR5(-/-) mice secrete lower amounts of IL-2, and a similar phenotype is observed in humans who lack CCR5 expression (CCR5-Delta32/Delta32 homozygotes) as well as after Ab-mediated blockade of CCR5 in human T cells genetically intact for CCR5 expression. Conversely, overexpression of CCR5 in human T cells results in enhanced IL-2 production. CCR5 surface levels correlate positively with IL-2 protein and mRNA abundance, suggesting that CCR5 affects IL-2 gene regulation. Signaling via CCR5 resulted in NFAT transactivation in T cells that was blocked by Abs against CCR5 agonists, suggesting a link between CCR5 and downstream pathways that influence IL-2 expression. Furthermore, murine T cells lacking CCR5 had reduced levels of intranuclear NFAT following activation. Accordingly, CCR5 expression also promoted IL-2-dependent events, including CD25 expression, STAT5 phosphorylation, and T cell proliferation. We therefore suggest that by influencing a NFAT-mediated pathway that regulates IL-2 production and IL-2-dependent events, CCR5 may play a critical role in T cell responses. In accord with our prior inferences from genetic-epidemiologic studies, such CCR5-dependent responses might constitute a viral entry-independent mechanism by which CCR5 may influence HIV-AIDS pathogenesis | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 7 | |a Interleukin-2 |2 NLM | |
| 650 | 7 | |a NFATC Transcription Factors |2 NLM | |
| 650 | 7 | |a Receptors, CCR5 |2 NLM | |
| 700 | 1 | |a Quinones, Marlon P |e verfasserin |4 aut | |
| 700 | 1 | |a Mummidi, Srinivas |e verfasserin |4 aut | |
| 700 | 1 | |a Srinivas, Sowmya |e verfasserin |4 aut | |
| 700 | 1 | |a Gaitan, Alvaro A |e verfasserin |4 aut | |
| 700 | 1 | |a Begum, Kazi |e verfasserin |4 aut | |
| 700 | 1 | |a Jimenez, Fabio |e verfasserin |4 aut | |
| 700 | 1 | |a VanCompernolle, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Unutmaz, Derya |e verfasserin |4 aut | |
| 700 | 1 | |a Ahuja, Seema S |e verfasserin |4 aut | |
| 700 | 1 | |a Ahuja, Sunil K |e verfasserin |4 aut | |
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| 912 | |a GBV_USEFLAG_A | ||
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| 951 | |a AR | ||
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