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Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment.

Wilson AD, Hicks C - Vet. Res. (2016)

Bottom Line: Transcription of IL17, which has been shown to have a regulatory function in human papillomavirus-associated tumours, was also elevated in equine sarcoids compared to spleen.In contrast, the levels of mRNA transcripts for effector T cell cytokines IL2, IL4 and interferon-gamma (IFNγ) were not elevated in sarcoids compared to healthy skin or spleen.Similarly neither interferon-alpha (IFNα), interferon-beta (IFNβ) nor IL12 family members were elevated in sarcoids compared to normal skin.

View Article: PubMed Central - PubMed

Affiliation: School of Veterinary Sciences, University of Bristol, Langford, Bristol, BS40 5DU, UK. doug.wilson@bris.ac.uk.

ABSTRACT
Bovine papillomavirus (BPV) infections of equine species have a central role in the aetiology of equine sarcoids; a common benign skin tumour of horses, zebras and donkeys. Within the lesions, all of the early papillomavirus genes are expressed and promote the excessive replication of fibroblasts which characterise these tumours. Equine sarcoids differ from BPV induced fibro-papillomas of cattle (the natural host of BPV), in that they do not produce high amounts of virus particles, do not usually regress spontaneously and do not sero-convert to BPV; features which suggest that affected horses lack an effective anti-viral immune response to BPV. Equine sarcoids contain large numbers of CD4+ CD8+ dual positive T-cells which uniformly express FOXP3, the key transcription factor of regulatory T-cells, and FOXP3 is also expressed within the BPV infected fibroblasts. Compared to healthy skin, sarcoids showed increased mRNA transcription for FOXP3 and the regulatory cytokine TGFβ. Transcription of IL17, which has been shown to have a regulatory function in human papillomavirus-associated tumours, was also elevated in equine sarcoids compared to spleen. In contrast, the levels of mRNA transcripts for effector T cell cytokines IL2, IL4 and interferon-gamma (IFNγ) were not elevated in sarcoids compared to healthy skin or spleen. Similarly neither interferon-alpha (IFNα), interferon-beta (IFNβ) nor IL12 family members were elevated in sarcoids compared to normal skin. We suggest that the regulatory cytokine micro-environment within sarcoids enables the persistence of the lesions by preventing an effective anti-viral immune response.

No MeSH data available.


Related in: MedlinePlus

Sarcoid MHC expression. Frozen sarcoid tissue stained with (A) Mouse monoclonal anti-equine MHC II. Goat anti-mouse FITC. B Rabbit anti CD3 donkey anti-rabbit Texas red (C) combined image with DAPI counterstain, the majority of MHC II expressing cells are CD3+ T-cells. D Mouse monoclonal anti-equine MHC I. Goat anti-mouse FITC. E Rabbit anti CD3 donkey anti-rabbit Texas red (F) combined image with DAPI counterstain the strongly MHC I positive cells are CD3+ T-cells. G Monoclonal anti-BPV E2 goat anti-mouse IgG1 FITC, (H) Monoclonal anti-equine MHC I goat anti mouse IgG2a. I Combined image with some possible E2 MHC I dual positive cells (arrow).
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Fig5: Sarcoid MHC expression. Frozen sarcoid tissue stained with (A) Mouse monoclonal anti-equine MHC II. Goat anti-mouse FITC. B Rabbit anti CD3 donkey anti-rabbit Texas red (C) combined image with DAPI counterstain, the majority of MHC II expressing cells are CD3+ T-cells. D Mouse monoclonal anti-equine MHC I. Goat anti-mouse FITC. E Rabbit anti CD3 donkey anti-rabbit Texas red (F) combined image with DAPI counterstain the strongly MHC I positive cells are CD3+ T-cells. G Monoclonal anti-BPV E2 goat anti-mouse IgG1 FITC, (H) Monoclonal anti-equine MHC I goat anti mouse IgG2a. I Combined image with some possible E2 MHC I dual positive cells (arrow).

Mentions: Both MHC class I and MHC class II antigens were expressed on a proportion of cells within sarcoids (Figure 5). Many of the MHC II positive cells co-expressed CD3 (Figures 5A, B and C), and given the variable and often weak intensity of CD3 staining it was difficult to determine the extent to which non T-cells expressing MHC II may be present in sarcoid tissues. Similarly MHC class I was also expressed most strongly on CD3 positive cells (Figures 5D, E and F). We next attempted to determine if MHC I was co-expressed on BPV E2 positive tumour cells (Figures 5G, H and I), some co-localisation of MHC I and BPV E2 was detected but is not possible to say whether this was due to membrane surface expression on MHC I on tumour fibroblasts.Figure 5


Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment.

Wilson AD, Hicks C - Vet. Res. (2016)

Sarcoid MHC expression. Frozen sarcoid tissue stained with (A) Mouse monoclonal anti-equine MHC II. Goat anti-mouse FITC. B Rabbit anti CD3 donkey anti-rabbit Texas red (C) combined image with DAPI counterstain, the majority of MHC II expressing cells are CD3+ T-cells. D Mouse monoclonal anti-equine MHC I. Goat anti-mouse FITC. E Rabbit anti CD3 donkey anti-rabbit Texas red (F) combined image with DAPI counterstain the strongly MHC I positive cells are CD3+ T-cells. G Monoclonal anti-BPV E2 goat anti-mouse IgG1 FITC, (H) Monoclonal anti-equine MHC I goat anti mouse IgG2a. I Combined image with some possible E2 MHC I dual positive cells (arrow).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4862206&req=5

Fig5: Sarcoid MHC expression. Frozen sarcoid tissue stained with (A) Mouse monoclonal anti-equine MHC II. Goat anti-mouse FITC. B Rabbit anti CD3 donkey anti-rabbit Texas red (C) combined image with DAPI counterstain, the majority of MHC II expressing cells are CD3+ T-cells. D Mouse monoclonal anti-equine MHC I. Goat anti-mouse FITC. E Rabbit anti CD3 donkey anti-rabbit Texas red (F) combined image with DAPI counterstain the strongly MHC I positive cells are CD3+ T-cells. G Monoclonal anti-BPV E2 goat anti-mouse IgG1 FITC, (H) Monoclonal anti-equine MHC I goat anti mouse IgG2a. I Combined image with some possible E2 MHC I dual positive cells (arrow).
Mentions: Both MHC class I and MHC class II antigens were expressed on a proportion of cells within sarcoids (Figure 5). Many of the MHC II positive cells co-expressed CD3 (Figures 5A, B and C), and given the variable and often weak intensity of CD3 staining it was difficult to determine the extent to which non T-cells expressing MHC II may be present in sarcoid tissues. Similarly MHC class I was also expressed most strongly on CD3 positive cells (Figures 5D, E and F). We next attempted to determine if MHC I was co-expressed on BPV E2 positive tumour cells (Figures 5G, H and I), some co-localisation of MHC I and BPV E2 was detected but is not possible to say whether this was due to membrane surface expression on MHC I on tumour fibroblasts.Figure 5

Bottom Line: Transcription of IL17, which has been shown to have a regulatory function in human papillomavirus-associated tumours, was also elevated in equine sarcoids compared to spleen.In contrast, the levels of mRNA transcripts for effector T cell cytokines IL2, IL4 and interferon-gamma (IFNγ) were not elevated in sarcoids compared to healthy skin or spleen.Similarly neither interferon-alpha (IFNα), interferon-beta (IFNβ) nor IL12 family members were elevated in sarcoids compared to normal skin.

View Article: PubMed Central - PubMed

Affiliation: School of Veterinary Sciences, University of Bristol, Langford, Bristol, BS40 5DU, UK. doug.wilson@bris.ac.uk.

ABSTRACT
Bovine papillomavirus (BPV) infections of equine species have a central role in the aetiology of equine sarcoids; a common benign skin tumour of horses, zebras and donkeys. Within the lesions, all of the early papillomavirus genes are expressed and promote the excessive replication of fibroblasts which characterise these tumours. Equine sarcoids differ from BPV induced fibro-papillomas of cattle (the natural host of BPV), in that they do not produce high amounts of virus particles, do not usually regress spontaneously and do not sero-convert to BPV; features which suggest that affected horses lack an effective anti-viral immune response to BPV. Equine sarcoids contain large numbers of CD4+ CD8+ dual positive T-cells which uniformly express FOXP3, the key transcription factor of regulatory T-cells, and FOXP3 is also expressed within the BPV infected fibroblasts. Compared to healthy skin, sarcoids showed increased mRNA transcription for FOXP3 and the regulatory cytokine TGFβ. Transcription of IL17, which has been shown to have a regulatory function in human papillomavirus-associated tumours, was also elevated in equine sarcoids compared to spleen. In contrast, the levels of mRNA transcripts for effector T cell cytokines IL2, IL4 and interferon-gamma (IFNγ) were not elevated in sarcoids compared to healthy skin or spleen. Similarly neither interferon-alpha (IFNα), interferon-beta (IFNβ) nor IL12 family members were elevated in sarcoids compared to normal skin. We suggest that the regulatory cytokine micro-environment within sarcoids enables the persistence of the lesions by preventing an effective anti-viral immune response.

No MeSH data available.


Related in: MedlinePlus