Engrafting Horse Immune Cells into Mouse Hosts for the Study of the Acute Equine Immune Responses.
Abstract: Immunological studies in the horse are frequently hampered by lack of environmental control, complicated study design, and ethical concerns when performing high risk studies. The purpose of the current study was to investigate the utility of a xenograft model for studying acute equine immune responses. Immunocompromised non obese diabetic (NOD). sudden combined immunodeficiency (scid).gamma-/- (NSG) mice were engrafted with either equine peripheral blood lymphocytes (PBLs) or equine bone marrow to determine an optimal protocol for equine lymphocyte engraftment. We found that both PBL and bone marrow grafts populated the host mice successfully. Bone marrow transplants were technically more challenging and required further processing to retard graft versus host disease. Graft vs host disease was apparent at 28 days post-PBL transfer and 56 days post-bone marrow transfer. The results of these studies support the use of mouse hosts to study acute equine immune responses and that different engraftment techniques can be used depending on the experimental design.
Publication Date: 2021-10-14 PubMed ID: 34679981PubMed Central: PMC8532756DOI: 10.3390/ani11102962Google 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.
- 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 the applicability of a xenograft model, particularly involving mouse hosts, for studying acute equine immune responses. The findings suggest that both equine peripheral blood lymphocytes and bone marrow can successfully populate host mice, and the onset of graft versus host disease can be controlled depending on the graft used.
Background and Purpose of the Study
- The study was conducted in light of the challenges inherent in directly studying horse immune reactions. These challenges include controlling environmental factors, designing apt studies, and ethical concerns related to risky procedures.
- Thus, the study’s primary aim was exploring the potential of a xenograft model, in which tissues or cells from one species (horse in this case) is implanted into an organism of another species (here, mice) for understanding acute equine immune responses.
Study Design and Methodology
- Immunodeficient non-obese diabetic (NOD) and severe combined immunodeficiency (scid).gamma-/- (NSG) mice were used as host subjects for this study.
- The researchers then grafted either equine peripheral blood lymphocytes (PBLs) or equine bone marrow into these mice to ascertain the optimal method for equine lymphocyte engraftment.
Results and Observations
- Both PBL and bone marrow grafts successfully populated the host mice, meaning that their immune responses could be studied in these organisms.
- However, it was observed that bone marrow transplants were technically more complex, requiring more processing to delay the onset of graft versus host disease (GVHD) – a condition that sometimes arises after a transplant, where the host immune system sees the new tissue as an alien and attacks it.
- GVHD was observed to occur around 28 days after the PBL transfer, and around 56 days after bone marrow transfer.
Conclusion
- The research thus validates the use of mouse xenograft models in studying horse immune responses, specifically acute responses.
- It also highlights that the technique of engraftment can vary based on the specifics of the experimental design, with each method having its own advantages and considerations.
Cite This Article
APA
Leeth C, Adkins J, Hay A, Bogers S, Potter A, Witonsky S, Zhu J.
(2021).
Engrafting Horse Immune Cells into Mouse Hosts for the Study of the Acute Equine Immune Responses.
Animals (Basel), 11(10), 2962.
https://doi.org/10.3390/ani11102962 Publication
Researcher Affiliations
- Department of Animal and Poultry Sciences, 175 West Campus Drive MC 0306, Litton Reaves Hall rm 300, Blacksburg, VA 24061, USA.
- Department of Animal and Poultry Sciences, 175 West Campus Drive MC 0306, Litton Reaves Hall rm 300, Blacksburg, VA 24061, USA.
- Department of Animal and Poultry Sciences, 175 West Campus Drive MC 0306, Litton Reaves Hall rm 300, Blacksburg, VA 24061, USA.
- Virginia Maryland College of Veterinary Medicine, 205 Duck Pond Drive, Blacksburg, VA 24061, USA.
- Department of Animal and Poultry Sciences, 175 West Campus Drive MC 0306, Litton Reaves Hall rm 300, Blacksburg, VA 24061, USA.
- Virginia Maryland College of Veterinary Medicine, 205 Duck Pond Drive, Blacksburg, VA 24061, USA.
- Department of Animal and Poultry Sciences, 175 West Campus Drive MC 0306, Litton Reaves Hall rm 300, Blacksburg, VA 24061, USA.
Grant Funding
- 1019507 / National Institute of Food and Agriculture
- 178626 / VMCVM Internal Research Competition
- n/a / Virginia Horse Industry Board
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 27 references
- Foote JB, Kabir FM, Graff EC, Cattley RC, DeInnocentes P, Smith BF, Bird RC. Engraftment of canine peripheral blood lymphocytes into nonobese diabetic-severe combined immune deficient IL-2R common gamma chain null mice.. Vet Immunol Immunopathol 2014 Feb 15;157(3-4):131-41.
- Greenwood JD, Croy BA. A study on the engraftment and trafficking of bovine peripheral blood leukocytes in severe combined immunodeficient mice.. Vet Immunol Immunopathol 1993 Sep;38(1-2):21-44.
- Greenwood JD, Croy BA, Trout DR, Wilcock BP. Xenogeneic (bovine) peripheral blood leukocytes engrafted into severe combined immunodeficient mice retain primary immune function.. Vet Immunol Immunopathol 1997 Oct 6;59(1-2):93-112.
- Petznek H, Kleiter M, Tichy A, Fuchs-Baumgartinger A, Hohenadl C. Murine xenograft model demonstrates significant radio-sensitising effect of liposomal doxorubicin in a combination therapy for Feline Injection Site Sarcoma.. Res Vet Sci 2014 Oct;97(2):386-90.
- Balson GA, Croy BA, Ross TL, Yager JA. Demonstration of equine immunoglobulin in sera from severe combined immunodeficiency/beige mice inoculated with equine lymphocytes.. Vet Immunol Immunopathol 1993 Dec;39(4):315-25.
- Shultz LD, Brehm MA, Garcia-Martinez JV, Greiner DL. Humanized mice for immune system investigation: progress, promise and challenges.. Nat Rev Immunol 2012 Nov;12(11):786-98.
- Laboratory T.J.. Frequently Asked NSG Questions. .
- Watanabe S, Terashima K, Ohta S, Horibata S, Yajima M, Shiozawa Y, Dewan MZ, Yu Z, Ito M, Morio T, Shimizu N, Honda M, Yamamoto N. Hematopoietic stem cell-engrafted NOD/SCID/IL2Rgamma null mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses.. Blood 2007 Jan 1;109(1):212-8.
- Akkina R, Berges BK, Palmer BE, Remling L, Neff CP, Kuruvilla J, Connick E, Folkvord J, Gagliardi K, Kassu A, Akkina SR. Humanized Rag1-/- γc-/- mice support multilineage hematopoiesis and are susceptible to HIV-1 infection via systemic and vaginal routes.. PLoS One 2011;6(6):e20169.
- Mian MF, Pek EA, Chenoweth MJ, Coombes BK, Ashkar AA. Humanized mice for Salmonella typhi infection: new tools for an old problem.. Virulence 2011 May-Jun;2(3):248-52.
- Libby SJ, Brehm MA, Greiner DL, Shultz LD, McClelland M, Smith KD, Cookson BT, Karlinsey JE, Kinkel TL, Porwollik S, Canals R, Cummings LA, Fang FC. Humanized nonobese diabetic-scid IL2rgammanull mice are susceptible to lethal Salmonella Typhi infection.. Proc Natl Acad Sci U S A 2010 Aug 31;107(35):15589-94.
- Dorner M, Rice CM, Ploss A. Study of hepatitis C virus entry in genetically humanized mice.. Methods 2013 Feb;59(2):249-57.
- Brehm MA, Powers AC, Shultz LD, Greiner DL. Advancing animal models of human type 1 diabetes by engraftment of functional human tissues in immunodeficient mice.. Cold Spring Harb Perspect Med 2012 May;2(5):a007757.
- Marx JO, Vudathala D, Murphy L, Rankin S, Hankenson FC. Antibiotic administration in the drinking water of mice.. J Am Assoc Lab Anim Sci 2014 May;53(3):301-6.
- Leeth CM, Racine J, Chapman HD, Arpa B, Carrillo J, Carrascal J, Wang Q, Ratiu J, Egia-Mendikute L, Rosell-Mases E, Stratmann T, Verdaguer J, Serreze DV. B-lymphocytes expressing an Ig specificity recognizing the pancreatic ß-cell autoantigen peripherin are potent contributors to type 1 diabetes development in NOD mice.. Diabetes 2016 Jul;65(7):1977-1987.
- Committee on Care and Use of Laboratory Animals. Guide for the care and use of laboratory animals. Washington, DC, USA: 1986.
- Zhu J, Hay AN, Potter AA, Richwine MW, Sproule T, LeRoith T, Wilson J, Hasham MG, Roopenian DC, Leeth CM. Abrogated AID Function Prolongs Survival and Diminishes Renal Pathology in the BXSB Mouse Model of Systemic Lupus Erythematosus.. J Immunol 2020 Mar 1;204(5):1091-1100.
- Ratiu JJ, Racine JJ, Hasham MG, Wang Q, Branca JA, Chapman HD, Zhu J, Donghia N, Philip V, Schott WH, Wasserfall C, Atkinson MA, Mills KD, Leeth CM, Serreze DV. Genetic and Small Molecule Disruption of the AID/RAD51 Axis Similarly Protects Nonobese Diabetic Mice from Type 1 Diabetes through Expansion of Regulatory B Lymphocytes.. J Immunol 2017 Jun 1;198(11):4255-4267.
- Korngold R, Sprent J. Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow.. J Exp Med 1978 Dec 1;148(6):1687-98.
- Morgan RA. Human tumor xenografts: the good, the bad, and the ugly.. Mol Ther 2012 May;20(5):882-4.
- Chuang HL, Chang YC, Huang YT, Liao JW, Kao PL, Chen YF, Lin BY, Lin YL, Chen TH, Wang YC. Establishment and Characterization of Feline Mammary Tumor Patient-Derived Xenograft Model.. Animals (Basel) 2021 Aug 12;11(8).
- Koga Y, Ochiai A. Systematic Review of Patient-Derived Xenograft Models for Preclinical Studies of Anti-Cancer Drugs in Solid Tumors.. Cells 2019 May 6;8(5).
- Canter RJ, Grossenbacher SK, Foltz JA, Sturgill IR, Park JS, Luna JI, Kent MS, Culp WTN, Chen M, Modiano JF, Monjazeb AM, Lee DA, Murphy WJ. Radiotherapy enhances natural killer cell cytotoxicity and localization in pre-clinical canine sarcomas and first-in-dog clinical trial.. J Immunother Cancer 2017 Dec 19;5(1):98.
- Pearson T, Greiner DL, Shultz LD. Creation of "humanized" mice to study human immunity.. Curr Protoc Immunol 2008 May;Chapter 15:15.21.1-15.21.21.
- Wunderlich M, Chou FS, Sexton C, Presicce P, Chougnet CA, Aliberti J, Mulloy JC. Improved multilineage human hematopoietic reconstitution and function in NSGS mice.. PLoS One 2018;13(12):e0209034.
- Collymore C, Giuliano F, Banks EK. Head Tilt in Immunodeficient Mice Due to Contamination of Drinking Water by Burkholderia gladioli.. J Am Assoc Lab Anim Sci 2019 Mar 1;58(2):246-250.
- Champlin R. T-cell depletion to prevent graft-versus-host disease after bone marrow transplantation.. Hematol Oncol Clin North Am 1990 Jun;4(3):687-98.
Citations
This article has been cited 1 times.- Lawrence P, Escudero-Pérez B. Henipavirus Immune Evasion and Pathogenesis Mechanisms: Lessons Learnt from Natural Infection and Animal Models.. Viruses 2022 Apr 29;14(5).
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists