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

Geherin, Skye A.; Lee, Michael H.; Wilson, Ronald P.; Debes, Gudrun F.

doi:10.1016/j.vetimm.2013.06.008

Cited by 19 publications

(21 citation statements)

References 63 publications

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“…The reason for this difference is unclear. The expression of bovine and ovine IL-17A by CD4+ve and WC-1+ve/γδT cell subsets is consistent with other studies using a combination of flow cytometry and ELISpot [43, 45]. Only 0.2% of total WC-1+ve/γδT cells from activated ovine PBMC expressed IL-17A in our study, whereas around 6% of total WC-1+ve/γδT cells were constitutively IL-17A+ve from skin-draining lymph.…”

Section: Discussionsupporting

confidence: 92%

“…Only 0.2% of total WC-1+ve/γδT cells from activated ovine PBMC expressed IL-17A in our study, whereas around 6% of total WC-1+ve/γδT cells were constitutively IL-17A+ve from skin-draining lymph. This difference is possibly reflective of the altered capacity for surveillance and mobilisation at the skin to cutaneous infection [45]. Our data show that activated bovine CD8+ve(dim) T cells also have the capacity to produce intracellular IL-17A, the first report of this phenomenon in ruminants, but consistent with reports of human CD8+ve T cells (reviewed by Srenathan et al [51]).…”

Section: Discussionsupporting

confidence: 88%

“…We therefore focussed on screening a panel of seven anti-human or anti-mouse IL-17A mabs for ability to detect cattle and sheep IL-17A intracellularly. One of these mabs (eBio64DEC17) has been reported to detect intracellular IL-17A in sheep lymphocytes [45] and cattle, sheep and goat PBMC [46]. In these previous studies the cross-reactivity is implied as there was no validation against a specific control where IL-17A was known to be expressed.…”

Section: Discussionmentioning

confidence: 99%

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Enhancing the toolbox to study IL-17A in cattle and sheep

Wattegedera

Corripio-Miyar

Pang

et al. 2017

Vet Res

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The development of methods to detect cytokine expression by T cell subsets in ruminants is fundamental to strategic development of new livestock vaccines for prevention of infectious diseases. It has been possible to detect T cell expression of IFN-γ, IL-4 and IL-10 in ruminants for many years but methods to detect expression of IL-17A are relatively limited. To address this gap in capability we have cloned bovine and ovine IL-17A cDNAs and expressed biologically-active recombinant proteins in Chinese Hamster Ovary (CHO) cells. We used the transfected CHO cells to screen commercially-available antibodies for their ability to detect IL-17A expression intracellularly and in culture supernates. We demonstrate that an ELISA for bovine IL-17A detects native ovine IL-17A. Moreover, the constituent polyclonal antibodies (pabs) in the ELISA were used to enumerate peripheral blood mononuclear cells (PBMC) expressing IL-17A from cattle and sheep by ELISpot. We identified two monoclonal antibodies (mabs) that detect recombinant intracellular IL-17A in CHO cells by flow cytometry. One of these mabs was used to detect native intracellular IL-17A expression in PBMC in conjunction with cell surface phenotyping mabs [CD4+ve, CD8+ve and Workshop Cluster 1 (WC-1)+ve gamma-delta (γδ)] we show that distinct T cell subsets in cattle (defined as CD4+ve, CD8+ve or WC-1+ve) and sheep (defined as CD4+ve or WC-1+ve) can express IL-17A following activation. These novel techniques provide a solid basis to investigate IL-17A expression and define specific CD4+ve T cell subset activation in ruminants.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-017-0426-5) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Enhancing the toolbox to study IL-17A in cattle and sheep

Wattegedera

Corripio-Miyar

Pang

et al. 2017

Vet Res

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“…Subsequently, samples were passed through a 100-μm cell strainer. The chemotaxis assay was carried out and analyzed as described (26). Briefly, 5×10 5 lymph-borne cells in RPMI 1640 containing 0.5% BSA were added to the upper chamber of 5-μm pore size Transwell inserts (Corning).…”

Section: Methodsmentioning

confidence: 99%

Effector T Cell Egress via Afferent Lymph Modulates Local Tissue Inflammation

Gómez

Diehl

Crosby

et al. 2015

The Journal of Immunology

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Memory/effector T cells recirculate through extralymphoid tissues by entering from blood and egressing via afferent lymph. While T cell entry into effector sites is key to inflammation, the relevance of T cell egress to this process is unknown. Here we found that antigen recognition at the effector site reduced the tissue egress of pro-inflammatory Th1 cells in a mouse model of delayed hypersensitivity. Transgenic expression of ‘tissue exit receptor’ CCR7 enhanced lymphatic egress of antigen-sequestered Th1 cells from the inflamed site and ameliorated inflammation. In contrast, lack of CCR7 on Th1 cells diminished their tissue egress while enhancing inflammation. Lymph-borne Th1 and Th17 cells draining the inflamed skin of sheep migrated toward the CCR7 ligand CCL21, suggesting the CCR7-CCL21 axis as a physiological target in regulating inflammation. In conclusion, exit receptors can be targeted to modulate T cell dwell time and inflammation at effector sites, revealing T cell tissue egress as a novel control point of inflammation.

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“…T cells in afferent lymph of both humans and sheep exhibit an effector-memory (T EM ) phenotype, characterized by elevated expression of common T cell activation markers, adhesion molecules, and effector cytokines (44, 45, 63, 64). Although γδ T cells are present in large numbers in afferent lymph from sheep (65), they are almost non-existent in lymph or blood in humans (63, 64) and so are not further discussed here.…”

Section: Cellular Composition Of Lymphmentioning

confidence: 99%

T Cell Trafficking through Lymphatic Vessels

2016

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T cell migration within and between peripheral tissues and secondary lymphoid organs is essential for proper functioning of adaptive immunity. While active T cell migration within a tissue is fairly slow, blood vessels and lymphatic vessels (LVs) serve as speedy highways that enable T cells to travel rapidly over long distances. The molecular and cellular mechanisms of T cell migration out of blood vessels have been intensively studied over the past 30 years. By contrast, less is known about T cell trafficking through the lymphatic vasculature. This migratory process occurs in one manner within lymph nodes (LNs), where recirculating T cells continuously exit into efferent lymphatics to return to the blood circulation. In another manner, T cell trafficking through lymphatics also occurs in peripheral tissues, where T cells exit the tissue by means of afferent lymphatics, to migrate to draining LNs and back into blood. In this review, we highlight how the anatomy of the lymphatic vasculature supports T cell trafficking and review current knowledge regarding the molecular and cellular requirements of T cell migration through LVs. Finally, we summarize and discuss recent insights regarding the presumed relevance of T cell trafficking through afferent lymphatics.

show abstract

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

Cited by 19 publications

References 63 publications

Enhancing the toolbox to study IL-17A in cattle and sheep

Enhancing the toolbox to study IL-17A in cattle and sheep

Effector T Cell Egress via Afferent Lymph Modulates Local Tissue Inflammation

T Cell Trafficking through Lymphatic Vessels

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