Printed Poster | Session 2

069 – Development of a New Humanised Mouse Model of Multiple Sclerosis Using NOD/LtSz-scid IL-2Rγc(null) Mice.

Rose-Marie Rebillard (1) – Lyne Bourbonnière (1) – Kathie Beland (2) – Elie Haddad (2) – Alexandre Prat (2)
CRCHUM, Département de neurosciences/Université de Montréal, Montreal, Canada (1) – Centre de recherche du CHUSJ, Département de microbiologie, infectiologie et immunologie/Université de Montréal, Montréal, Canada (2)

Introduction: Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for the study of multiple sclerosis (MS). Although instrumental in MS research, this model fails to replicate some characteristics of this highly complex demyelinating disease. Our hypothesis is that we can develop an innovative humanized mouse model of MS that can replicate the human pathology more accurately, which would be instrumental in achieving a better understanding of the disease and in facilitating the identification of novel therapeutic targets.
Methods: Peripheral blood mononuclear cells (PBMC) from MS patients and healthy donors were injected intraperitoneally into NOD/LtSz-scid IL-2Rγc(null) (NSG) mice in order to achieve immune reconstitution. 25 or 32 days following injection, immune cells were isolated from both CNS and spleen of each mouse and analyzed by flow cytometry. Data analysis was performed using a conventional gating strategy as well as using the unbiased t-SNE algorithm.
Results: Immune reconstitution was observed in all mice that received PBMC from either MS patients or healthy donors. No differences were found in the absolute number (between 1.02 x104 and 1.18 x 106 immune cells, mostly human leucocytes) or immunophenotype of CNS infiltrating cells between both groups. We did however find a significantly higher proportion of GM-CSF and IFNg expressing cells among CNS-infiltrating lymphocytes in comparison to those isolated from the spleen.
Conclusion: The intraperitoneal injection of MS patient PBMC into NSG mice alone is not sufficient to reproduce pathological features of MS in this mouse model. Nevertheless, we established that in this model, the immunophenotype of infiltrating immune cells is organ-specific, with CNS-infiltrating cells having a more inflammatory profile than cells isolated from the spleen, thereby confirming the major potential of using NSG mice in humanized models of neurological disease.