Engrafting Horse Immune Cells into Mouse Hosts for the Study of the Acute Equine Immune Responses.

Caroline Leeth,Sophie Bogers,Ashley Potter,Janie Adkins,Alayna Hay,Sharon Witonsky,Jing Zhu

doi:10.3390/ani11102962

Abstract

Simple SummaryFor decades, studies using research mice as models for disease have been critical to our current understanding of disease processes and associated immune responses, highlighting the ways in which mouse physiology is different from human and other species. Recent work has been directed at creating mice that can host human immune cells, allowing the study and manipulation of the human immune response without harm to patients. The purpose of this study was to explore to use of mouse hosts for horse immune cells. Horses are difficult to study immunologically as they are expensive to keep, and keeping their environment free of immune triggers is very difficult. Using mice allows us to increase our study numbers and control the environment which improves study reproducibility. In this study, we transferred both horse blood lymphocytes as well as horse bone marrow into specially modified mouse hosts. We found that mice are able to host horse immune cells and that these transferred cells are active. Future work can now build on this study to understand the horse immune response to infectious agents using mice, helping to identify new therapeutic tools to help equine patients.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.

Highlights

Equine immunological studies are frequently plagued by small sample populations, diverse patient populations, and the limited ability to control the research environment.Efforts to improve these limitations using equine subjects invariably results in exorbitant experimental costs as well as potentially raising ethical concerns
NSG recipient mice engrafted with equine peripheral blood leukocytes were followed for four weeks with two mice engrafted for each of three equine donors (Figure 1)
To assess the functional capacity of the transferred equine lymphocytes, splenic cells from the remaining mice surviving at 28 days nificant differences were found (Figure 3E)

Summary

Introduction

Equine immunological studies are frequently plagued by small sample populations, diverse patient populations, and the limited ability to control the research environment. Efforts to improve these limitations using equine subjects invariably results in exorbitant experimental costs as well as potentially raising ethical concerns. Basic research must be performed on the equine immune response to determine its unique profile. Through this specific knowledge can we hope to improve health and novel therapeutic development for the equine population. Over the past several decades, the xenograft field has made great strides, successfully engrafting mouse hosts with tissues from other species. The NOD.Cg-Prkdcscid Il2rgtm1Wjl /SzJ (NOD.scid.gamma or NSG)

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