TNF-α-Induced Secretion of C-C Chemokines Modulates C-C Chemokine Receptor 5 Expression on Peripheral Blood Lymphocytes

Hornung, Felicita; Scala, Giuseppe; Lenardo, Michael J.

doi:10.4049/jimmunol.164.12.6180

Cited by 56 publications

(52 citation statements)

References 72 publications

(59 reference statements)

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“…The expression of chemokine receptors is modulated by cellular activation, which can result in up-regulation (45)(46)(47)(48)(49) or downmodulation (50). Not unexpectedly (50), CCR5 expression on ex vivo-analyzed ␥␦ T cells was dramatically down-regulated by activation of PBMC with PHA or M. tb.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Chemokine Receptor Expression on Peripheral Blood γδ T Lymphocytes: Strong Expression of CCR5 Is a Selective Feature of Vδ2/Vγ9 γδ T Cells

Glatzel

Wesch

Schiemann

et al. 2002

The Journal of Immunology

141

145

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γδ T lymphocytes play an important role in the immune defense against infection, based on the unique reactivity of human Vδ2Vγ9 γδ T cells toward bacterial phosphoantigens. Chemokines and their corresponding receptors orchestrate numerous cellular reactions, including leukocyte migration, activation, and degranulation. In this study we investigated the expression of various receptors for inflammatory and homeostatic chemokines on peripheral blood γδ T cells and compared their expression patterns with those on αβ T cells. Although several of the analyzed receptors (including CCR6, CCR7, CXCR4, and CXCR5) were not differentially expressed on γδ vs αβ T cells, γδ T cells expressed strongly increased levels of the RANTES/macrophage inflammatory protein-1α/-1β receptor CCR5 and also enhanced levels of CCR1–3 and CXCR1–3. CCR5 expression was restricted to Vδ2 γδ T cells, while the minor subset of Vδ1 γδ T cells preferentially expressed CXCR1. Stimulation with heat-killed extracts of Mycobacterium tuberculosis down-modulated cell surface expression of CCR5 on γδ T cells in a macrophage-dependent manner, while synthetic phosphoantigen isopentenyl pyrophosphate and CCR5 ligands directly triggered CCR5 down-modulation on γδ T cells. The functionality of chemokine receptors CCR5 and CXCR3 on γδ T cells was demonstrated by Ca2+ mobilization and chemotactic response to the respective chemokines. Our results identify high level expression of CCR5 as a characteristic and selective feature of circulating Vδ2 γδ T cells, which is in line with their suspected function as Th1 effector T cells.

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Section: Discussionmentioning

confidence: 99%

Patterns of Chemokine Receptor Expression on Peripheral Blood γδ T Lymphocytes: Strong Expression of CCR5 Is a Selective Feature of Vδ2/Vγ9 γδ T Cells

Glatzel

Wesch

Schiemann

et al. 2002

The Journal of Immunology

141

145

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“…A similar phenomenon has been observed in experimental mycobacterial infection (Jacobs et al, 2000), where TNFR2 deficiency resulted in a modest increase in susceptibility to infection, but did not alter T cell responses to mycobacterial antigen. TNFR2 is known to mediate upregulated expression of C-C chemokines such as macrophage-inflammatory protein (MIP)-1α, MIP-1β, and regulated by activation, normal T cell expressed and secreted (RANTES) chemokine by T cells in an NF-κB-dependent manner (Hornung et al, 2000). Impaired expression of these chemokines as a result of TNFR2 deficiency might negatively impact recruitment of cells to granulomas, explaining the delayed granuloma phenotype observed in TNFR1 −/− /R2 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Involvement of TNF in limiting liver pathology and promoting parasite survival during schistosome infection

Davies

Lim

Blank

et al. 2004

International Journal for Parasitology

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CD4 + T cell responses and macrophage activation are essential components of schistosome egginduced granuloma formation. Previous studies implicated tumour necrosis factor (TNF) as a potential mediator of macrophage recruitment and activation during schistosome infection. Here we demonstrate that signalling by TNF and its receptors can influence granuloma formation, but is ultimately dispensable for granuloma formation in this system. However, we identify a previously unrecognised role for TNF in limiting hepatocellular damage in response to schistosome eggs. Further, we show that this activity of TNF is independent of TNF receptors (TNFR1 and TNFR2). Taken together, these data suggest that additional, as yet unrecognised receptors exist for TNF and that these receptors are capable of mediating important pathological effects in the liver. Finally, we provide evidence that TNF plays an unexpected role in maintaining adult schistosome viability in the portal system.

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“…TNF is known to increase expression of both receptors 17,18 TNF also increases the expression of the CCR2 receptor on Th2 lymphocytes, 19 as well as of CC-chemokine ligand4 that is chemotactic for eosinophils. 20 The above-mentioned genes and interactions represent only a small part of those included in the seven topscoring networks. Moreover, these networks were chosen from a total of 50 networks that were identified as significant.…”

Section: Proliferation Of Th2 Cells Following Allergen Stimulationmentioning

confidence: 99%

A network-based analysis of allergen-challenged CD4+ T cells from patients with allergic rhinitis

Benson

Carlsson²,

Guillot

et al. 2006

Genes Immun

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We performed a network-based analysis of DNA microarray data from allergen-challenged CD4 þ T cells from patients with seasonal allergic rhinitis. Differentially expressed genes were organized into a functionally annotated network using the Ingenuity Knowledge Database, which is based on manual review of more than 200 000 publications. The main function of this network is the regulation of lymphocyte apoptosis, a role associated with several genes of the tuber necrosis factor superfamily. The expression of TNFRSF4, one of the genes in this family, was found to be 48 times higher in allergen-challenged cells than in diluent-challenged cells. TNFRSF4 is known to inhibit apoptosis and to enhance Th2 proliferation. Examination of a different material of allergen-stimulated peripheral blood mononuclear cells showed a higher number of interleukin-4 þ type 2 CD4 þ T (Th2) cells in patients than in controls (Po0.01), as well as a higher number of non-apoptotic Th2 cells in patients (Po0.01). The number of Th2 cells expressing TNFRSF4, TNFSF7 and TNFRSF1B was also significantly higher in patients. Treatment with anti-TNFSF4 resulted in a significantly decreased number of Th2 cells (Po0.05). A logical inference from all this is that the proliferation of allergen-challenged Th2 cells is associated with a decreased apoptosis of Th2 cells and an increase in TNFRSF4 signalling.

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TNF-α-Induced Secretion of C-C Chemokines Modulates C-C Chemokine Receptor 5 Expression on Peripheral Blood Lymphocytes

Cited by 56 publications

References 72 publications

Patterns of Chemokine Receptor Expression on Peripheral Blood γδ T Lymphocytes: Strong Expression of CCR5 Is a Selective Feature of Vδ2/Vγ9 γδ T Cells

Patterns of Chemokine Receptor Expression on Peripheral Blood γδ T Lymphocytes: Strong Expression of CCR5 Is a Selective Feature of Vδ2/Vγ9 γδ T Cells

Involvement of TNF in limiting liver pathology and promoting parasite survival during schistosome infection

A network-based analysis of allergen-challenged CD4+ T cells from patients with allergic rhinitis

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