Both T and B cells are indispensable for the development of a PBMC transfer-induced humanized mouse model for SSc.
Arthritis Res Ther
; 24(1): 209, 2022 08 25.
Article
em En
| MEDLINE
| ID: mdl-36008863
ABSTRACT
BACKGROUND:
Recently, a novel humanized mouse model for systemic sclerosis (SSc) was established by transferring peripheral blood mononuclear cells (PBMC) from patients with SSc to Rag2-/-Il2rg-/- immunodeficient mice. Here, we aimed to investigate the role of T and B cells in this humanized mouse model.METHODS:
T and B cells were depleted in vitro from freshly isolated PBMC using anti-CD3 and anti-CD19 magnetic microbeads, respectively. Subsequently, PBMC and T or B cell-depleted PBMC were transferred into Rag2-/-/Il2rg-/- mice via intraperitoneal injection. Twelve weeks after the transfer, mice were sacrificed and evaluated.RESULTS:
Mice transferred with whole PBMC from SSc patients developed systemic inflammation in the lungs, kidneys, and liver, and 6 out of 11 mice died or had to be sacrificed during the experiment. By contrast, such inflammation and death were not observed in mice transferred with corresponding T or B cell-depleted PBMC. In line with this finding, transfer with whole PBMC restored the splenic white pulp composing of human T, B, and plasma cells and led to the production of a considerable amount of human autoantibodies in recipient mice, while those immunological features were rarely observed in mice that received T or B cell-depleted PBMC. In contrast to our previous findings demonstrating a transfer of the protective effect of a B cell therapy into the mouse, treatment of SSc patients with chemical immunosuppressive drugs did not affect the pathogenicity of PBMC.CONCLUSIONS:
This study demonstrates that both T and B cells are indispensable for the pathogenesis of the PBMC transfer-induced mouse model for SSc.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Escleroderma Sistêmico
/
Leucócitos Mononucleares
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article