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Veterinary ophthalmology2019; 23(1); 160-170; doi: 10.1111/vop.12704

Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro.

Abstract: Equine recurrent uveitis (ERU) is an immune-mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many species, making them a potential therapeutic option for ERU. The objectives of this study were to define the lymphocyte phenotype of horses with ERU and to determine how MSCs alter T-cell phenotype in vitro. Whole blood was taken from 7 horses with ERU and 10 healthy horses and peripheral blood mononuclear cells were isolated. The markers CD21, CD3, CD4, and CD8 were used to identify lymphocyte subsets while CD25, CD62L, Foxp3, IFNγ, and IL10 were used to identify T-cell phenotype. Adipose-derived MSCs were expanded, irradiated (to control proliferation), and incubated with CD4+ T-cells from healthy horses, after which lymphocytes were collected and analyzed via flow cytometry. The percentages of T-cells and B-cells in horses with ERU were similar to normal horses. However, CD4+ T-cells from horses with ERU expressed higher amounts of IFNγ indicating a pro-inflammatory Th1 phenotype. When co-incubated with MSCs, activated CD4+ T-cells reduced expression of CD25, CD62L, Foxp3, and IFNγ. MSCs had a lesser ability to decrease activation when cell-cell contact or prostaglandin signaling was blocked. MSCs continue to show promise as a treatment for ERU as they decreased the CD4+ T-cell activation phenotype through a combination of cell-cell contact and prostaglandin signaling.
© 2019 The Authors. Veterinary Ophthalmology published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Ophthalmologists.
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Publication Date: 2019-08-22 PubMed ID: 31441218PubMed Central: PMC6980227DOI: 10.1111/vop.12704Google Scholar: Lookup
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  • Journal Article

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 investigates equine recurrent uveitis (ERU), a disease causing continuous or repeated inflammation in horses which can result in blindness. The paper explores how mesenchymal stem cells can alter the activation of immune cells, potentially providing a therapeutic approach to this currently incurable disease.

Disease and Treatment Strategy

  • ERU is an immune-mediated disease that creates repeated or ongoing inflammatory episodes which can lead to blindness in horses. At the moment, there isn’t any successful cure.
  • There is a possibility that mesenchymal stem cells (MSCs) could be used as a treatment. MSCs have been found to reduce immune cell activation in many species when tested in vitro (outside of a live organism).

Study Objectives and Methodology

  • The study aimed to define the lymphocyte phenotype in horses with ERU, and to discover how MSCs change the T-cell phenotype in vitro.
  • Blood was taken from 7 horses diagnosed with ERU and 10 healthy horses. This blood was used to isolate peripheral blood mononuclear cells.
  • Several markers were used to identify lymphocyte subsets and T-cell phenotype.
  • The collected CD4+ T-cells from healthy horses were incubated with expanded, irradiated (to control proliferation) adipose-derived MSCs, after which the lymphocytes were collected and analyzed.

Findings

  • The study found that the percentages of T-cells and B-cells were not different between horses with ERU and healthy ones.
  • However, CD4+ T-cells from horses suffering from ERU expressed more IFNγ, indicating a pro-inflammatory Th1 phenotype. This means that these cells could be contributing to the persistent inflammation found in ERU.
  • When CD4+ T-cells were exposed to MSCs, they showed decreased expression of CD25, CD62L, Foxp3, and IFNγ – meaning they were less activated and less pro-inflammatory.
  • The potential of MSCs to decrease activation was found to be reduced when cell-to-cell contact or prostaglandin signaling was blocked, suggesting the importance of these pathways in MSC-induced immune modulation.

Implications

  • The research implies that MSCs continue to hold promise as a potential treatment for ERU. They diminished the activation of CD4+ T-cells, which could contribute to dampening the recurrent inflammation in ERU.
  • The study also highlights the importance of cell-to-cell contact and prostaglandin signaling in enabling MSCs to decrease immune cell activation.

Cite This Article

APA
Saldinger LK, Nelson SG, Bellone RR, Lassaline M, Mack M, Walker NJ, Borjesson DL. (2019). Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro. Vet Ophthalmol, 23(1), 160-170. https://doi.org/10.1111/vop.12704

Publication

Veterinary ophthalmology
ISSN: 1463-5224
NlmUniqueID: 100887377
Country: England
Language: English
Volume: 23
Issue: 1
Pages: 160-170

Researcher Affiliations

Saldinger, Laurel K
  • Department of Pathology, Microbiology and Immunology, Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, California.
Nelson, Seldy G
  • Department of Pathology, Microbiology and Immunology, Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, California.
Bellone, Rebecca R
  • Department of Population Health and Reproduction, Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, California.
Lassaline, Mary
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California.
Mack, Maura
  • Department of Population Health and Reproduction, Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, California.
Walker, Naomi J
  • Department of Pathology, Microbiology and Immunology, Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, California.
Borjesson, Dori L
  • Department of Pathology, Microbiology and Immunology, Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, California.

MeSH Terms

  • Animals
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Gene Expression Regulation
  • Horse Diseases / pathology
  • Horses
  • Interferon-gamma
  • Interleukin-2 Receptor alpha Subunit
  • L-Selectin / genetics
  • L-Selectin / metabolism
  • Mesenchymal Stem Cells / physiology
  • Uveitis / pathology
  • Uveitis / veterinary

Grant Funding

  • T35 OD010956 / NIH HHS
  • Center for Equine Health at UC Davis
  • T35 OD010956-19 / NIH Clinical Center

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Citations

This article has been cited 17 times.
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