Functional Expression of the Chemokine Receptor CCR5 on Virus Epitope-Specific Memory and Effector CD8+ T Cells

Fukada, Katsuhiko; Sobao, Yuji; Tomiyama, Hiroko; Oka, Shinichi; Takiguchi, Masafumi

doi:10.4049/jimmunol.168.5.2225

Cited by 109 publications

(126 citation statements)

References 34 publications

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“…CCR7 -CD8 + T cells are mature memory (memory/effector) or effector cells. In addition, CCR5 is dominantly expressed on memory CD8 + T cells with the phenotype CD27 + CD28 + CD45RA -, and its expression is down-regulated during the maturation into effector cells [7,15,27]. These findings suggest and CCR7 on CD8 + cells was examined using anti-CD8, anti-CCR5, anti-CCR7 and anti-CXCR4 mAb, or mouse IgG mAb as negative control.…”

Section: Discussionmentioning

confidence: 92%

“…The correlation between the expression of CXCR4 and CCR7 or CCR5 on CD8 + T cells CCR7 is expressed on naive CD8 + T cells and a portion of memory CD8 + T cells [7,15,21,22], while CCR5 is predominantly expressed on memory CD8 + T cells and a some effector CD8 + T cells [15,23,27]. These observations suggest that the expression of CXCR4 is positively correlated with that of CCR7, but is not correlated with that of CCR5.…”

Section: 3mentioning

confidence: 99%

“…4B). We hypothesized that the CCR5 -CXCR4 high population includes CCR7 + naive and central memory CD8 + T cells, because they express high level of CXCR4 but not CCR5 [7,15,27], and that other CCR5CXCR4 populations include both memory/effector and effector T cells. To investigate these CCR7/CXCR4 and CCR5/CXCR4 populations in detail, we directly analyzed the expression of these three receptors on CD8 + T cells from the same individual using three mAb specific for CXCR4, CCR5, and CCR7.…”

Section: 3mentioning

confidence: 99%

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Down‐regulation of CXCR4 expression on human CD8⁺ T cells during peripheral differentiation

et al. 2004

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Multi-color flow cytometric analysis on human CD8 + T cell subsets revealed that CXCR4 is predominantly expressed on CD8 + T cells with the naive CD27 + CD28 + CD45RA + phenotype, and is down-regulated during differentiation into those with an effector phenotype. The downregulation of CXCR4 expression during peripheral differentiation was supported by the fact that the expression of CXCR4 on CD8 + T cells was negatively correlated with that of perforin. The analysis of CCR5, CCR7, and CXCR4 co-expression further showed that CD8 + T cells expressing a high level of CXCR4 are CCR7 + CCR5 -naive or central memory subsets, and those expressing a low level of CXCR4 were included in the CCR7 -CCR5 +/-memory/effector and effector subsets. Epstein Barr virus-specific CD8 + T cells, which mostly express the memory phenotype, expressed CXCR4, while human cytomegalovirus-specific CD8 + T cells, which mostly express the effector phenotype, partially expressed this receptor, showing that the expression of CXCR4 is also down-regulated during differentiation of viral antigenspecific CD8 + T cells. The classification of human CD8 + T cells based on the expression of these chemokine receptors should prove useful for studies that clarify the differentiation of human CD8 + T cells.

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Section: Discussionmentioning

confidence: 92%

Section: 3mentioning

confidence: 99%

Section: 3mentioning

confidence: 99%

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Down‐regulation of CXCR4 expression on human CD8⁺ T cells during peripheral differentiation

et al. 2004

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“…CD4ϩ,CD28 null T cells have lost their classic helper function because of an accompanying inability to up-regulate CD40 ligand (18), but they have acquired granzyme and perforin that impart cytotoxicity (19). They also have large cytoplasmic stores of interferon-␥ (20), express the chemokine receptor CCR5 (21), and up-regulate CD161 (22), a molecule that facilitates tissue invasion. Hence, CD4ϩ,CD28 null T cells are equipped to infiltrate sites of inflammation, where they amplify local inflammatory and autoimmune cascades (22,23).…”

Section: Conclusion Overproduction Of Tnf␣ In Ra Induces a Global Domentioning

confidence: 99%

Modulation of CD28 expression with anti–tumor necrosis factor α therapy in rheumatoid arthritis

Bryl¹,

Vallejo²,

Matteson³

et al. 2005

Arthritis & Rheumatism

125

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Objective. The immune system of patients with rheumatoid arthritis (RA) is characterized by the accumulation of CD4؉ T cells deficient in CD28 expression and the up-regulation of tumor necrosis factor ␣ (TNF␣). Previous in vitro studies have shown that TNF␣ induces transcriptional silencing of the CD28 gene. Because reduced expression of CD28 in T cells compromises immunocompetence, we examined whether CD28 expression is reduced in patients with RA in vivo and whether the reduction is related to TNF␣.Methods. Patients with RA and age-matched individuals were recruited. Peripheral blood mononuclear cells were stained for CD3, CD4, CD8, CD28, TNF receptor I (TNFRI), and TNFRII, and analyzed by quantitative flow cytometry. The number of CD28 and TNFR molecules was monitored in a subgroup of patients with RA undergoing treatment with anti-TNF␣.Results. In addition to higher frequencies of CD28 null T cells, patients with RA had significantly reduced numbers of CD28 and TNFRI molecules on CD4؉,CD28؉ T cells. Normal expression could be restored in vitro by overnight culture, suggesting that CD28 in patients was modulated by exogenous factors. In contrast, treatment with TNF␣ in vitro resulted in further down-regulation. CD28 expression was normalized in patients undergoing TNF␣-neutralizing therapy.Conclusion. Overproduction of TNF␣ in RA induces a global down-regulation of CD28 in CD4؉ T cells and may cause reduced sensitivity to costimulatory signals in T cell responses.

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“…Some express the C-type lectin receptor CD161 that is known to facilitate tissue invasion. Still others also express the inflammatory chemokine receptor CCR5 (16). Clearly, CD28-null T cells are armed to invade sites of inflammation where they participate in maladaptive immune responses (17).…”

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confidence: 99%

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

Michel

Turesson

Lemster

et al. 2007

Arthritis & Rheumatism

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Objective. T cells deficient in CD28 expression have been implicated in the pathogenesis of rheumatoid arthritis (RA). Given that CD28-null T cells are functionally heterogeneous, we undertook this study to screen for novel receptors on these cells.Methods. Seventy-two patients with RA (ages 35-84 years) and 53 healthy persons (32 young controls ages 19-34 years, 21 older controls ages 39-86 years) were recruited. Phenotypes and proliferative capacity of T cells from fresh leukocytes and of long-term cultures were monitored by flow cytometry. Lung biopsy specimens from patients with RA-associated interstitial pneumonitis (IP) were examined by immunohistochemistry. Receptor functionality was assessed by crosslinking bioassays.Results. Chronic stimulation of CD28؉ T cells in vitro yielded progenies that lacked CD28 but that gained CD56. Ex vivo analysis of leukocytes from patients with extraarticular RA showed a higher frequency of CD56؉,CD28-null T cells than in patients with disease confined to the joints or in healthy controls. CD56؉,CD28-null T cells had nil capacity for proliferation, consistent with cellular senescence. CD56؉ T cells had skewed T cell receptor (TCR) ␣/␤-chain usage and restricted TCR third complementarity-determining region spectra. Histologic studies showed that CD56؉ T cells were components of cellular infiltrates in RAassociated IP. CD56 crosslinking on T cells sufficiently induced cytokine production, although CD56/TCR coligation induced higher production levels.Conclusion. Chronic activation of T cells induces counterregulation of CD28 and CD56 expression. The loss of CD28 is accompanied by the gain of CD56 that confers TCR-independent and TCR-dependent activation pathways. We propose that accumulation of CD56؉ T cells in RA contributes to maladaptive immune responses and that CD56؉ T cells are potential targets for therapy.

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Functional Expression of the Chemokine Receptor CCR5 on Virus Epitope-Specific Memory and Effector CD8+ T Cells

Cited by 109 publications

References 34 publications

Down‐regulation of CXCR4 expression on human CD8⁺ T cells during peripheral differentiation

Down‐regulation of CXCR4 expression on human CD8⁺ T cells during peripheral differentiation

Modulation of CD28 expression with anti–tumor necrosis factor α therapy in rheumatoid arthritis

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

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Functional Expression of the Chemokine Receptor CCR5 on Virus Epitope-Specific Memory and Effector CD8+ T Cells

Cited by 109 publications

References 34 publications

Down‐regulation of CXCR4 expression on human CD8+ T cells during peripheral differentiation

Down‐regulation of CXCR4 expression on human CD8+ T cells during peripheral differentiation

Modulation of CD28 expression with anti–tumor necrosis factor α therapy in rheumatoid arthritis

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

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Down‐regulation of CXCR4 expression on human CD8⁺ T cells during peripheral differentiation

Down‐regulation of CXCR4 expression on human CD8⁺ T cells during peripheral differentiation