γδ T Cell Homing to Skin and Migration to Skin-Draining Lymph Nodes Is CCR7 Independent

Vrieling, Manouk; Santema, Wiebren J.; Rhijn, Ildiko Van; Rutten, Victor P.M.G.; Koets, Ad P.

doi:10.4049/jimmunol.1101972

Cited by 37 publications

(35 citation statements)

References 51 publications

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“…Interestingly, unlike co-isolated ovine CD4 T cells, γδ T cells traveling in the skin draining lymph were unresponsive to ligands for CCR4, CCR8, CCR10, typical skin-attracting chemokines (Bromley et al, 2008). Our data contrast the finding that bovine skin draining γδ T cells express low transcripts of CCR4 and CCR10 (Vrieling et al, 2012). As mRNA expression does not always correlate with functional chemokine receptor expression, it is possible that bovine γδ T cells also lack responsiveness to CCR4 and CCR10 ligands.…”

Section: Discussioncontrasting

confidence: 99%

“…3). These findings are in line with a recent study, showing that bovine γδ T cells in the skin-draining afferent lymph lack CCR7 (Vrieling et al, 2012) and with findings in the mouse that exclude a role for CCR7 in dermal γδ T cell homeostasis (Sumaria et al, 2011). Interestingly, during the chronic phase of inflammation, mouse αβ T cells can also exit the skin independently of CCR7 (Brown et al, 2010).…”

Section: Discussionsupporting

confidence: 92%

“…Taken together, we conclude that unlike dendritic cells, ovine skin-draining γδ T cells lack sufficient expression of key molecules that define professional APCs. Additional data support that γδ T cells in afferent lymph of ruminants are not traveling to draining lymph nodes to activate αβ T cells in the T-cell zone, because these γδ T cells rapidly pass through the lymph node to re-enter the efferent lymph (Young et al, 2000) and recirculate back into skin (Mackay and Hein, 1989; Vrieling et al, 2012). …”

Section: Discussionmentioning

confidence: 84%

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Ovine skin-recirculating γδ T cells express IFN-γ and IL-17 and exit tissue independently of CCR7

Geherin

Lee

Wilson

et al. 2013

Veterinary Immunology and Immunopathology

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γδ T cells continuously survey extralymphoid tissues, providing key effector functions during infection and inflammation. Despite their importance, the function and the molecules that drive migration of skin-recirculating γδ T cells are poorly described. Here we found that γδ T cells traveling in the skin-draining afferent lymph of sheep are effectors that produce IFN-γ or IL-17 and express high levels of the skin- and inflammation-seeking molecule E-selectin ligand. Consistent with a role for chemokine receptor CCR7 in mediating T cell exit from extralymphoid tissues, conventional CD4 and CD8 T cells in skin-draining lymph were enriched in their expression of CCR7 compared to their skin-residing counterparts. In contrast, co-isolated γδ T cells in skin or lymph lacked expression of CCR7, indicating that they use alternative receptors for egress. Skin-draining γδ T cells were unresponsive to many cutaneous and inflammatory chemokines, including ligands for CCR2, CCR4, CCR5, CCR8, CCR10, and CXCR3, but showed selective chemotaxis toward the cutaneously expressed CCR6 ligand CCL20. Moreover, IL-17+ γδ T cells were the most CCL20-responsive subset of γδ T cells. The data suggest that γδ T cells survey the skin and sites of inflammation and infection, entering via CCR6 and E-selectin ligand and leaving independent of the CCR7-CCL21 axis.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

Ovine skin-recirculating γδ T cells express IFN-γ and IL-17 and exit tissue independently of CCR7

Geherin

Lee

Wilson

et al. 2013

Veterinary Immunology and Immunopathology

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“…Once the virus is internalized through the fin bases, the dermis layer of the skin constitutes one of the primary replication sites within this area (Montero et al, 2011), and although the chemokine response in this area seems to be limited in response to the virus (Montero et al, 2011), all evidence points to the fact that CCR7 is not implicated in recruiting lymphocytes to the skin. In bovine, γgδ T cells in the skin are shown to recirculate from the blood through the skin back into the afferent and efferent lymph within in a CCR7-independent fashion (Vrieling et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

Identification of a novel CCR7 gene in rainbow trout with differential expression in the context of mucosal or systemic infection

Ordás¹,

Castro²,

Dixon³

et al. 2012

Developmental & Comparative Immunology

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In mammals, CCR7 is the chemokine receptor for the CCL19 and CCL21 chemokines, molecules with a major role in the recruitment of lymphocytes to lymph nodes and Peyer's patches in the intestinal mucosa, especially naïve T lymphocytes. In the current work, we have identified a CCR7 orthologue in rainbow trout (Oncorhynchus mykiss) that shares many of the conserved features of mammalian CCR7. The receptor is constitutively transcribed in the gills, hindgut, spleen, thymus and gonad. When leukocyte populations were isolated, IgM+ cells, T cells and myeloid cells from head kidney transcribed the CCR7 gene. In blood, both IgM+ and IgT+ B cells and myeloid cells but not T lymphocytes were transcribing CCR7, whereas in the spleen, CCR7 mRNA expression was strongly detected in T lymphocytes. In response to infection with viral hemorrhagic septicemia virus (VHSV), CCR7 transcription was down-regulated in spleen and head kidney upon intraperitoneal infection, whereas upon bath infection, CCR7 was up-regulated in gills but remained undetected in the fin bases, the main site of virus entry. Concerning its regulation in the intestinal mucosa, the ex vivo stimulation of hindgut segments with Poly I:C or inactivated bacteria significantly increased CCR7 transcription, while in the context of an infection with Ceratomyxa shasta, the levels of transcription of CCR7 in both IgM+ and IgT+ cells from the gut were dramatically increased. All these data suggest that CCR7 plays an important role in lymphocyte trafficking during rainbow trout infections, in which CCR7 appears to be implicated in the recruitment of B lymphocytes into the gut.

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“…Efferent lymphatic vessels of five male British Holstein‐Friesian ( B. taurus ) calves aged 3–6 months old were surgically cannulated at APHA using a method described previously 28. Samples of PB were taken during the cannulation period by jugular venepuncture into 10‐ml vacutainers containing sodium heparin (10 U/ml).…”

Section: Methodsmentioning

confidence: 99%

Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood

et al. 2017

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SummaryNatural killer (NK) cells are widely distributed in lymphoid and non‐lymphoid tissues, but little is known about the recirculation of NK cells between blood and tissues. This is relevant to understanding recirculation in the steady‐state and also for determining the roles for NK cells in vaccine‐induced immunity and responses to infection. Therefore, the percentage of NK cells and their phenotype across peripheral blood, afferent lymph and lymph nodes in steady‐state conditions was investigated in cattle using the pseudo‐afferent lymphatic cannulation model. CD2+ CD25lo NK cells were the predominant subset of NK cells within the blood. In contrast, CD2− CD25hi NK cells were the main subset present within the skin‐draining afferent lymphatic vessels and lymph nodes, indicating that CD2− NK cells are the principal NK cell subset trafficking to lymph nodes via the afferent lymphatic vessel. Furthermore, a low percentage of NK cells were present in efferent lymph, which were predominantly of the CD2− subset, indicating that NK cells can egress from lymph nodes and return to circulation in steady‐state conditions. These compartmentalization data indicate that NK cells represent a population of recirculating lymphocytes in steady‐state conditions and therefore may be important during immune responses to vaccination or infection.

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γδ T Cell Homing to Skin and Migration to Skin-Draining Lymph Nodes Is CCR7 Independent

Cited by 37 publications

References 51 publications

Ovine skin-recirculating γδ T cells express IFN-γ and IL-17 and exit tissue independently of CCR7

Ovine skin-recirculating γδ T cells express IFN-γ and IL-17 and exit tissue independently of CCR7

Identification of a novel CCR7 gene in rainbow trout with differential expression in the context of mucosal or systemic infection

Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood

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