FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Vet Res / Both tumour cells and infiltrating T-cells in equine sarcoid...
Veterinary research2016; 47(1); 55; doi: 10.1186/s13567-016-0339-8

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

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.
Get Full Text
Publication Date: 2016-05-09 PubMed ID: 27160146PubMed Central: PMC4862206DOI: 10.1186/s13567-016-0339-8Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explored the behavior of tumour cells and T-cells in equine sarcoids, a common skin tumor in horses, associated with Bovine papillomavirus infections. Specifically, the large presence of a key immune regulator, FOXP3, and certain cytokines suggest an immune-suppressed environment within these tumors that prevents an effective anti-viral response.

Understanding Equine Sarcoids and FOXP3

  • The study focusses on equine sarcoids, benign skin tumors commonly seen in horses, donkeys, and zebras. These sarcoids are linked to Bovine papillomavirus (BPV) infections.
  • The research highlights that all early papillomavirus gene expressions within the sarcoids promote excessive fibroblasts replication, a common characteristic of these tumors.
  • Unlike BPV-induced fibro-papillomas in cattle, equine sarcoids do not produce virus particles and generally do not regress or convert to BPV – indicating an ineffective anti-viral immune response.
  • The highlight of the study is the uniform expression of FOXP3, a key transcription factor of regulatory T-cells, found in both the T-cells and BPV infected fibroblasts within the sarcoids.
  • FOXP3, associated with immune suppression, might be playing a critical role in the persistence of these equine sarcoids.

Cytokine Microenvironment Inside The Sarcoids

  • Upon comparing sarcoids and healthy skin, the former showed an increased mRNA transcription for both FOXP3 and regulatory cytokine, TGFβ, indicating an immune-suppressed environment.
  • Elevated transcription of IL17, associated with regulatory functions in human papillomavirus-related tumors, was also found in equine sarcoids.
  • Contrary to the elevation in regulatory elements, no heightened mRNA transcripts levels for effector T cell cytokines – IL2, IL4, and interferon-gamma (IFNγ) were found. These elements usually promote immunity.
  • The study mentioned the absence of elevated mRNA transcripts levels for interferon-alpha (IFNα), interferon-beta (IFNβ), and IL12 family elements in sarcoids, compared to healthy skin.
  • The research suggests that the micro-environment within sarcoids, high in regulatory cytokines, might be preventing an effective anti-viral immune response, thereby promoting the persistence of equine sarcoids.

Cite This Article

APA
Wilson AD, Hicks C. (2016). Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment. Vet Res, 47(1), 55. https://doi.org/10.1186/s13567-016-0339-8

Publication

Veterinary research
ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English
Volume: 47
Issue: 1
Pages: 55
PII: 55

Researcher Affiliations

Wilson, A Douglas
  • School of Veterinary Sciences, University of Bristol, Langford, Bristol, BS40 5DU, UK. doug.wilson@bris.ac.uk.
Hicks, Chelsea
  • School of Veterinary Sciences, University of Bristol, Langford, Bristol, BS40 5DU, UK.

MeSH Terms

  • Animals
  • Cytokines / metabolism
  • Cytokines / physiology
  • Forkhead Transcription Factors / metabolism
  • Horse Diseases / immunology
  • Horse Diseases / metabolism
  • Horse Diseases / virology
  • Horses
  • Papillomaviridae
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / veterinary
  • Papillomavirus Infections / virology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / veterinary
  • Skin Neoplasms / virology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology
  • Tumor Microenvironment / immunology

References

This article includes 70 references
  1. Gottschling M, Göker M, Stamatakis A, Bininda-Emonds OR, Nindl I, Bravo IG. Quantifying the phylodynamic forces driving papillomavirus evolution.. Mol Biol Evol 2011 Jul;28(7):2101-13.
    doi: 10.1093/molbev/msr030pubmed: 21285031google scholar: lookup
  2. Marais HJ, Page PC. Treatment of equine sarcoid in seven Cape mountain zebra (Equus zebra zebra).. J Wildl Dis 2011 Oct;47(4):917-24.
    doi: 10.7589/0090-3558-47.4.917pubmed: 22102662google scholar: lookup
  3. Jarret WHF. The natural history of bovine papillomavirus infections. In: G K, editor. advances in viral oncology. New York: Raven; 1985. pp. 83–102.
  4. Nasir L, McFarlane ST, Torrontegui BO, Reid SW. Screening for bovine papillomavirus in peripheral blood cells of donkeys with and without sarcoids.. Res Vet Sci 1997 Nov-Dec;63(3):289-90.
    doi: 10.1016/S0034-5288(97)90036-9pubmed: 9491459google scholar: lookup
  5. Martens A, De Moor A, Demeulemeester J, Ducatelle R. Histopathological characteristics of five clinical types of equine sarcoid.. Res Vet Sci 2000 Dec;69(3):295-300.
    doi: 10.1053/rvsc.2000.0432pubmed: 11124103google scholar: lookup
  6. Sironi G, Caniatti M, Scanziani E. Immunohistochemical detection of papillomavirus structural antigens in animal hyperplastic and neoplastic epithelial lesions.. Zentralbl Veterinarmed A 1990 Dec;37(10):760-70.
    doi: 10.1111/j.1439-0442.1990.tb00970.xpubmed: 1963721google scholar: lookup
  7. Sundberg JP, Junge RE, Lancaster WD. Immunoperoxidase localization of papillomaviruses in hyperplastic and neoplastic epithelial lesions of animals.. Am J Vet Res 1984 Jul;45(7):1441-6.
    pubmed: 24049914
  8. Tajima M, Gordon DE, Olson C. Electron microscopy of bovine papilloma and deer fibroma viruses.. Am J Vet Res 1968 Jun;29(6):1185-94.
    pubmed: 4297856
  9. Wilson AD, Armstrong ELR, Gofton RG, Mason J, De Toit N, Day MJ. Characterisation of early and late bovine papillomavirus protein expression in equine sarcoids.. Vet Microbiol 2013 Mar 23;162(2-4):369-380.
    doi: 10.1016/j.vetmic.2012.10.010pubmed: 23123175google scholar: lookup
  10. OLSON C Jr, COOK RH. Cutaneous sarcoma-like lesions of the horse caused by the agent of bovine papilloma.. Proc Soc Exp Biol Med 1951 Jun;77(2):281-4.
    doi: 10.3181/00379727-77-18750pubmed: 14854020google scholar: lookup
  11. Ragland WL, Spencer GR. Attempts to relate bovine papilloma virus to the cause of equine sarcoid: equidae inoculated intradermally with bovine papilloma virus.. Am J Vet Res 1969 May;30(5):743-52.
    pubmed: 5813668
  12. Lee KP, Olson C. Response of calves to intravenous and repeated intradermal inoculation of bovine papilloma virus.. Am J Vet Res 1968 Nov;29(11):2103-12.
    pubmed: 4300967
  13. Voss JL. Transmission of equine sarcoid.. Am J Vet Res 1969 Feb;30(2):183-91.
    pubmed: 5392976
  14. Barthold SW, Olson C. Fibroma regression in relation to antibody and challenge immunity to bovine papilloma virus.. Cancer Res 1974 Oct;34(10):2436-31.
    pubmed: 4370021
  15. Bergvall KE. Sarcoids.. Vet Clin North Am Equine Pract 2013 Dec;29(3):657-71.
    doi: 10.1016/j.cveq.2013.09.002pubmed: 24267682google scholar: lookup
  16. Ragland WL, Spencer GR. Attempts to relate bovine papilloma virus to the cause of equine sarcoid: immunity to bovine papilloma virus.. Am J Vet Res 1968 Jul;29(7):1363-6.
    pubmed: 4298397
  17. SEGRE D, OLSON C Jr, HOERLEIN AB. Neutralization of bovine papilloma virus with serums from cattle and horses with experimental papillomas.. Am J Vet Res 1955 Oct;16(61 Part 1):517-20.
    pubmed: 13259027
  18. Amtmann E, Müller H, Sauer G. Equine connective tissue tumors contain unintegrated bovine papilloma virus DNA.. J Virol 1980 Sep;35(3):962-4.
    pmc: PMC288890pubmed: 6252350doi: 10.1128/jvi.35.3.962-964.1980google scholar: lookup
  19. Brandt S, Tober R, Corteggio A, Burger S, Sabitzer S, Walter I, Kainzbauer C, Steinborn R, Nasir L, Borzacchiello G. BPV-1 infection is not confined to the dermis but also involves the epidermis of equine sarcoids.. Vet Microbiol 2011 May 12;150(1-2):35-40.
    doi: 10.1016/j.vetmic.2010.12.021pubmed: 21242040google scholar: lookup
  20. Borzacchiello G, Russo V, Della Salda L, Roperto S, Roperto F. Expression of platelet-derived growth factor-beta receptor and bovine papillomavirus E5 and E7 oncoproteins in equine sarcoid.. J Comp Pathol 2008 Nov;139(4):231-7.
    doi: 10.1016/j.jcpa.2008.07.006pubmed: 18814884google scholar: lookup
  21. Carr EA, Théon AP, Madewell BR, Hitchcock ME, Schlegel R, Schiller JT. Expression of a transforming gene (E5) of bovine papillomavirus in sarcoids obtained from horses.. Am J Vet Res 2001 Aug;62(8):1212-7.
    doi: 10.2460/ajvr.2001.62.1212pubmed: 11497440google scholar: lookup
  22. Nasir L, Reid SW. Bovine papillomaviral gene expression in equine sarcoid tumours.. Virus Res 1999 Jun;61(2):171-5.
    doi: 10.1016/S0168-1702(99)00022-2pubmed: 10475087google scholar: lookup
  23. Jelínek F, Tachezy R. Cutaneous papillomatosis in cattle.. J Comp Pathol 2005 Jan;132(1):70-81.
    doi: 10.1016/j.jcpa.2004.07.001pubmed: 15629481google scholar: lookup
  24. Lory S, von Tscharner C, Marti E, Bestetti G, Grimm S, Waldvogel A. In situ hybridisation of equine sarcoids with bovine papilloma virus.. Vet Rec 1993 Feb 6;132(6):132-3.
    doi: 10.1136/vr.132.6.132pubmed: 8383371google scholar: lookup
  25. Wobeser BK, Hill JE, Jackson ML, Kidney BA, Mayer MN, Townsend HG, Allen AL. Localization of Bovine papillomavirus in equine sarcoids and inflammatory skin conditions of horses using laser microdissection and two forms of DNA amplification.. J Vet Diagn Invest 2012 Jan;24(1):32-41.
    doi: 10.1177/1040638711425952pubmed: 22362933google scholar: lookup
  26. Gaynor AM, Zhu KW, Dela Cruz FN Jr, Affolter VK, Pesavento PA. Localization of Bovine Papillomavirus Nucleic Acid in Equine Sarcoids.. Vet Pathol 2016 May;53(3):567-73.
    doi: 10.1177/0300985815594852pubmed: 26215759google scholar: lookup
  27. Brandt S, Haralambus R, Shafti-Keramat S, Steinborn R, Stanek C, Kirnbauer R. A subset of equine sarcoids harbours BPV-1 DNA in a complex with L1 major capsid protein.. Virology 2008 Jun 5;375(2):433-41.
    doi: 10.1016/j.virol.2008.02.014pubmed: 18395238google scholar: lookup
  28. Trewby H, Ayele G, Borzacchiello G, Brandt S, Campo MS, Del Fava C, Marais J, Leonardi L, Vanselow B, Biek R, Nasir L. Analysis of the long control region of bovine papillomavirus type 1 associated with sarcoids in equine hosts indicates multiple cross-species transmission events and phylogeographical structure.. J Gen Virol 2014 Dec;95(Pt 12):2748-2756.
    doi: 10.1099/vir.0.066589-0pmc: PMC4233631pubmed: 25185436google scholar: lookup
  29. Chambers G, Ellsmore VA, O'Brien PM, Reid SW, Love S, Campo MS, Nasir L. Sequence variants of bovine papillomavirus E5 detected in equine sarcoids.. Virus Res 2003 Oct;96(1-2):141-5.
    doi: 10.1016/S0168-1702(03)00175-8pubmed: 12951274google scholar: lookup
  30. Marchetti B, Gault EA, Cortese MS, Yuan Z, Ellis SA, Nasir L, Campo MS. Bovine papillomavirus type 1 oncoprotein E5 inhibits equine MHC class I and interacts with equine MHC I heavy chain.. J Gen Virol 2009 Dec;90(Pt 12):2865-2870.
    doi: 10.1099/vir.0.014746-0pubmed: 19675187google scholar: lookup
  31. Yuan ZQ, Bennett L, Campo MS, Nasir L. Bovine papillomavirus type 1 E2 and E7 proteins down-regulate Toll Like Receptor 4 (TLR4) expression in equine fibroblasts.. Virus Res 2010 Apr;149(1):124-7.
    doi: 10.1016/j.virusres.2010.01.008pubmed: 20109504google scholar: lookup
  32. Mählmann K, Hamza E, Marti E, Dolf G, Klukowska J, Gerber V, Koch C. Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.. Vet J 2014 Dec;202(3):516-21.
    doi: 10.1016/j.tvjl.2014.09.003pubmed: 25266649google scholar: lookup
  33. Kurg R, Parik J, Juronen E, Sedman T, Abroi A, Liiv I, Langel U, Ustav M. Effect of bovine papillomavirus E2 protein-specific monoclonal antibodies on papillomavirus DNA replication.. J Virol 1999 Jun;73(6):4670-7.
    pmc: PMC112508pubmed: 10233926doi: 10.1128/jvi.73.6.4670-4677.1999google scholar: lookup
  34. Pittaway CE, Lawson AL, Coles GC, Wilson AD. Systemic and mucosal IgE antibody responses of horses to infection with Anoplocephala perfoliata.. Vet Parasitol 2014 Jan 17;199(1-2):32-41.
    doi: 10.1016/j.vetpar.2013.10.005pubmed: 24183646google scholar: lookup
  35. Primer3web version 4.0.0. www.bioinfo.ut.ee
  36. mFold www.bioinfo.rpi.edu
  37. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes.. Genome Biol 2002 Jun 18;3(7):RESEARCH0034.
    doi: 10.1186/gb-2002-3-7-research0034pmc: PMC126239pubmed: 12184808google scholar: lookup
  38. de Zoeten EF, Lee I, Wang L, Chen C, Ge G, Wells AD, Hancock WW, Ozkaynak E. Foxp3 processing by proprotein convertases and control of regulatory T cell function.. J Biol Chem 2009 Feb 27;284(9):5709-16.
    doi: 10.1074/jbc.M807322200pmc: PMC2645825pubmed: 19117830google scholar: lookup
  39. Ziegler SF. FOXP3: of mice and men.. Annu Rev Immunol 2006;24:209-26.
    doi: 10.1146/annurev.immunol.24.021605.090547pubmed: 16551248google scholar: lookup
  40. Reid SW, Gettinby G, Fowler JN, Ikin P. Epidemiological observations on sarcoids in a population of donkeys (Equus asinus).. Vet Rec 1994 Feb 26;134(9):207-11.
    doi: 10.1136/vr.134.9.207pubmed: 8171807google scholar: lookup
  41. Ragland WL, Keown GH, Gorham JR. An epizootic of equine sarcoid.. Nature 1966 Jun 25;210(5043):1399.
    doi: 10.1038/2101399a0pubmed: 6007121google scholar: lookup
  42. Haralambus R, Burgstaller J, Klukowska-Rötzler J, Steinborn R, Buchinger S, Gerber V, Brandt S. Intralesional bovine papillomavirus DNA loads reflect severity of equine sarcoid disease.. Equine Vet J 2010 May;42(4):327-31.
    doi: 10.1111/j.2042-3306.2010.00078.xpubmed: 20525051google scholar: lookup
  43. Bogaert L, Van Poucke M, De Baere C, Dewulf J, Peelman L, Ducatelle R, Gasthuys F, Martens A. Bovine papillomavirus load and mRNA expression, cell proliferation and p53 expression in four clinical types of equine sarcoid.. J Gen Virol 2007 Aug;88(Pt 8):2155-2161.
    doi: 10.1099/vir.0.82876-0pubmed: 17622617google scholar: lookup
  44. Christen G, Gerber V, Dolf G, Burger D, Koch C. Inheritance of equine sarcoid disease in Franches-Montagnes horses.. Vet J 2014 Jan;199(1):68-71.
    doi: 10.1016/j.tvjl.2013.09.053pubmed: 24152383google scholar: lookup
  45. Lazary S, Marti E, Szalai G, Gaillard C, Gerber H. Studies on the frequency and associations of equine leucocyte antigens in sarcoid and summer dermatitis.. Anim Genet 1994 Jun;25 Suppl 1:75-80.
    doi: 10.1111/j.1365-2052.1994.tb00406.xpubmed: 7943987google scholar: lookup
  46. Broström H. Equine sarcoids. A clinical and epidemiological study in relation to equine leucocyte antigens (ELA).. Acta Vet Scand 1995;36(2):223-36.
    pmc: PMC8095413pubmed: 7484549doi: 10.1186/bf03547691google scholar: lookup
  47. Jandova V, Klukowska-Rötzler J, Dolf G, Janda J, Roosje P, Marti E, Koch C, Gerber V, Swinburne J. Whole genome scan identifies several chromosomal regions linked to equine sarcoids.. Schweiz Arch Tierheilkd 2012 Jan;154(1):19-25.
    doi: 10.1024/0036-7281/a000288pubmed: 22222899google scholar: lookup
  48. Mattil-Fritz S, Scharner D, Piuko K, Thönes N, Gissmann L, Müller H, Müller M. Immunotherapy of equine sarcoid: dose-escalation trial for the use of chimeric papillomavirus-like particles.. J Gen Virol 2008 Jan;89(Pt 1):138-147.
    doi: 10.1099/vir.0.83266-0pubmed: 18089737google scholar: lookup
  49. Ashrafi GH, Piuko K, Burden F, Yuan Z, Gault EA, Müller M, Trawford A, Reid SWJ, Nasir L, Campo MS. Vaccination of sarcoid-bearing donkeys with chimeric virus-like particles of bovine papillomavirus type 1.. J Gen Virol 2008 Jan;89(Pt 1):148-157.
    doi: 10.1099/vir.0.83267-0pubmed: 18089738google scholar: lookup
  50. Germain RN. Maintaining system homeostasis: the third law of Newtonian immunology.. Nat Immunol 2012 Oct;13(10):902-6.
    doi: 10.1038/ni.2404pmc: PMC3518435pubmed: 22990887google scholar: lookup
  51. Vignali DA, Kuchroo VK. IL-12 family cytokines: immunological playmakers.. Nat Immunol 2012 Jul 19;13(8):722-8.
    doi: 10.1038/ni.2366pmc: PMC4158817pubmed: 22814351google scholar: lookup
  52. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells.. Annu Rev Immunol 2009;27:485-517.
    doi: 10.1146/annurev.immunol.021908.132710pubmed: 19132915google scholar: lookup
  53. Gosmann C, Mattarollo SR, Bridge JA, Frazer IH, Blumenthal A. IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.. J Immunol 2014 Sep 1;193(5):2248-57.
    doi: 10.4049/jimmunol.1400216pmc: PMC4135400pubmed: 25063870google scholar: lookup
  54. Cao Y, Zhao J, Lei Z, Shen S, Liu C, Li D, Liu J, Shen GX, Zhang GM, Feng ZH, Huang B. Local accumulation of FOXP3+ regulatory T cells: evidence for an immune evasion mechanism in patients with large condylomata acuminata.. J Immunol 2008 Jun 1;180(11):7681-6.
    doi: 10.4049/jimmunol.180.11.7681pubmed: 18490771google scholar: lookup
  55. Näsman A, Romanitan M, Nordfors C, Grün N, Johansson H, Hammarstedt L, Marklund L, Munck-Wikland E, Dalianis T, Ramqvist T. Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer.. PLoS One 2012;7(6):e38711.
    doi: 10.1371/journal.pone.0038711pmc: PMC3373553pubmed: 22701698google scholar: lookup
  56. Molling JW, de Gruijl TD, Glim J, Moreno M, Rozendaal L, Meijer CJ, van den Eertwegh AJ, Scheper RJ, von Blomberg ME, Bontkes HJ. CD4(+)CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia.. Int J Cancer 2007 Oct 15;121(8):1749-55.
    doi: 10.1002/ijc.22894pubmed: 17582606google scholar: lookup
  57. van Esch EM, van Poelgeest MI, Kouwenberg S, Osse EM, Trimbos JB, Fleuren GJ, Jordanova ES, van der Burg SH. Expression of coinhibitory receptors on T cells in the microenvironment of usual vulvar intraepithelial neoplasia is related to proinflammatory effector T cells and an increased recurrence-free survival.. Int J Cancer 2015 Feb 15;136(4):E95-106.
    doi: 10.1002/ijc.29174pubmed: 25220367google scholar: lookup
  58. Hamza E, Gerber V, Steinbach F, Marti E. Equine CD4(+) CD25(high) T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro.. Immunology 2011 Nov;134(3):292-304.
    doi: 10.1111/j.1365-2567.2011.03489.xpmc: PMC3209569pubmed: 21977999google scholar: lookup
  59. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance.. Cell 2008 May 30;133(5):775-87.
    doi: 10.1016/j.cell.2008.05.009pubmed: 18510923google scholar: lookup
  60. Ramsdell F, Ziegler SF. FOXP3 and scurfy: how it all began.. Nat Rev Immunol 2014 May;14(5):343-9.
    doi: 10.1038/nri3650pubmed: 24722479google scholar: lookup
  61. Hinz S, Pagerols-Raluy L, Oberg HH, Ammerpohl O, Grüssel S, Sipos B, Grützmann R, Pilarsky C, Ungefroren H, Saeger HD, Klöppel G, Kabelitz D, Kalthoff H. Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer.. Cancer Res 2007 Sep 1;67(17):8344-50.
    doi: 10.1158/0008-5472.CAN-06-3304pubmed: 17804750google scholar: lookup
  62. Ebert LM, Tan BS, Browning J, Svobodova S, Russell SE, Kirkpatrick N, Gedye C, Moss D, Ng SP, MacGregor D, Davis ID, Cebon J, Chen W. The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells.. Cancer Res 2008 Apr 15;68(8):3001-9.
    doi: 10.1158/0008-5472.CAN-07-5664pubmed: 18413770google scholar: lookup
  63. Zeng C, Yao Y, Jie W, Zhang M, Hu X, Zhao Y, Wang S, Yin J, Song Y. Up-regulation of Foxp3 participates in progression of cervical cancer.. Cancer Immunol Immunother 2013 Mar;62(3):481-7.
    doi: 10.1007/s00262-012-1348-8pubmed: 22986453google scholar: lookup
  64. Parel Y, Aurrand-Lions M, Scheja A, Dayer JM, Roosnek E, Chizzolini C. Presence of CD4+CD8+ double-positive T cells with very high interleukin-4 production potential in lesional skin of patients with systemic sclerosis.. Arthritis Rheum 2007 Oct;56(10):3459-67.
    doi: 10.1002/art.22927pubmed: 17907151google scholar: lookup
  65. Nascimbeni M, Pol S, Saunier B. Distinct CD4+ CD8+ double-positive T cells in the blood and liver of patients during chronic hepatitis B and C.. PLoS One 2011;6(5):e20145.
    doi: 10.1371/journal.pone.0020145pmc: PMC3102078pubmed: 21647449google scholar: lookup
  66. Das G, Augustine MM, Das J, Bottomly K, Ray P, Ray A. An important regulatory role for CD4+CD8 alpha alpha T cells in the intestinal epithelial layer in the prevention of inflammatory bowel disease.. Proc Natl Acad Sci U S A 2003 Apr 29;100(9):5324-9.
    doi: 10.1073/pnas.0831037100pmc: PMC154344pubmed: 12695566google scholar: lookup
  67. Zuckermann FA. Extrathymic CD4/CD8 double positive T cells.. Vet Immunol Immunopathol 1999 Dec 15;72(1-2):55-66.
    doi: 10.1016/S0165-2427(99)00118-Xpubmed: 10614493google scholar: lookup
  68. Silva-Campa E, Mata-Haro V, Mateu E, Hernández J. Porcine reproductive and respiratory syndrome virus induces CD4+CD8+CD25+Foxp3+ regulatory T cells (Tregs).. Virology 2012 Aug 15;430(1):73-80.
    doi: 10.1016/j.virol.2012.04.009pubmed: 22609353google scholar: lookup
  69. Bendali-Ahcène S, Cadore JL, Fontaine M, Monier JC. Anti-alpha chain monoclonal antibodies of equine MHC class-II antigens: applications to equine infectious anaemia.. Res Vet Sci 1997 Mar-Apr;62(2):99-104.
    doi: 10.1016/S0034-5288(97)90128-4pubmed: 9243705google scholar: lookup
  70. Holling TM, Schooten E, van Den Elsen PJ. Function and regulation of MHC class II molecules in T-lymphocytes: of mice and men.. Hum Immunol 2004 Apr;65(4):282-90.
    doi: 10.1016/j.humimm.2004.01.005pubmed: 15120183google scholar: lookup

Citations

This article has been cited 3 times.
  1. Jindra C, Hainisch EK, Brandt S. Immunotherapy of Equine Sarcoids-From Early Approaches to Innovative Vaccines. Vaccines (Basel) 2023 Mar 30;11(4).
    doi: 10.3390/vaccines11040769pubmed: 37112681google scholar: lookup
  2. Alkayyal AA. Insights from veterinary models for advancing oncolytic virotherapy through comparative oncology. Front Mol Biosci 2025;12:1615393.
    doi: 10.3389/fmolb.2025.1615393pubmed: 40475753google scholar: lookup
  3. Tinkler SH, Villa L, Manfredi MT, Walshe N, Jahns H. First report of Besnoitia bennetti in Irish donkeys: an emerging parasitic disease in Europe. Ir Vet J 2024 Feb 14;77(1):2.
    doi: 10.1186/s13620-024-00263-2pubmed: 38355717google scholar: lookup
Subscribe to our newsletter
Join 99,359 horse owners like you who receive our email updates on horse health and nutrition.