Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells

Helle Jensen; Lasse Folkersen; Søren Skov

doi:10.1371/journal.pone.0041577

Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4⁺ T-cells

Helle Jensen, Lasse Folkersen, Søren Skov

7 Citations (Scopus)

Abstract

NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8⁺ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4⁺ T-cells, however recently a subset of NKG2D⁺ CD4⁺ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D⁺ CD4⁺ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D⁺ CD4⁺ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4⁺ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D⁺ CD4⁺ T-cells, generated from HCMV-primed CD4⁺ T-cells. We show that the HCMV-primed NKG2D⁺ CD4⁺ T-cells possess a higher differentiated phenotype than the NKG2D^- CD4⁺ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4⁺ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4⁺ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4⁺ T-cells, whereas it is produced de novo in resting CD4⁺ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D⁺ CD4⁺ T-cells, as well as the mechanisms regulating NKG2D cell surface expression.

Original language	English
Journal	P L o S One
Volume	7
Issue number	8
Number of pages	14
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0041577
Publication status	Published - 1 Aug 2012

Keywords

CD4-Positive T-Lymphocytes
Cytomegalovirus
Female
Gene Expression Profiling
Gene Expression Regulation
Gene Knockdown Techniques
Genome-Wide Association Study
Humans
Lymphocyte Activation
Male
NK Cell Lectin-Like Receptor Subfamily D
NK Cell Lectin-Like Receptor Subfamily K
Signal Transduction

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title = "Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells",

abstract = "NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4+ T-cells, however recently a subset of NKG2D+ CD4+ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D+ CD4+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D+ CD4+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D+ CD4+ T-cells, generated from HCMV-primed CD4+ T-cells. We show that the HCMV-primed NKG2D+ CD4+ T-cells possess a higher differentiated phenotype than the NKG2D- CD4+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4+ T-cells, whereas it is produced de novo in resting CD4+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D+ CD4+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression.",

keywords = "CD4-Positive T-Lymphocytes, Cytomegalovirus, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Knockdown Techniques, Genome-Wide Association Study, Humans, Lymphocyte Activation, Male, NK Cell Lectin-Like Receptor Subfamily D, NK Cell Lectin-Like Receptor Subfamily K, Signal Transduction",

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T1 - Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells

AU - Jensen, Helle

AU - Folkersen, Lasse

AU - Skov, Søren

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N2 - NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4+ T-cells, however recently a subset of NKG2D+ CD4+ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D+ CD4+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D+ CD4+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D+ CD4+ T-cells, generated from HCMV-primed CD4+ T-cells. We show that the HCMV-primed NKG2D+ CD4+ T-cells possess a higher differentiated phenotype than the NKG2D- CD4+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4+ T-cells, whereas it is produced de novo in resting CD4+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D+ CD4+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression.

AB - NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4+ T-cells, however recently a subset of NKG2D+ CD4+ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D+ CD4+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D+ CD4+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D+ CD4+ T-cells, generated from HCMV-primed CD4+ T-cells. We show that the HCMV-primed NKG2D+ CD4+ T-cells possess a higher differentiated phenotype than the NKG2D- CD4+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4+ T-cells, whereas it is produced de novo in resting CD4+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D+ CD4+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression.

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KW - Cytomegalovirus

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Gene Knockdown Techniques

KW - Genome-Wide Association Study

KW - Humans

KW - Lymphocyte Activation

KW - Male

KW - NK Cell Lectin-Like Receptor Subfamily D

KW - NK Cell Lectin-Like Receptor Subfamily K

KW - Signal Transduction

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DO - 10.1371/journal.pone.0041577

M3 - Journal article

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SN - 1932-6203

VL - 7

JO - PLoS Computational Biology

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