Differential depletion of total T cells and regulatory T cells and prolonged allotransplant survival in CD3Æ humanized mice treated with polyclonal anti human thymocyte globulin.
PLoS One
; 12(3): e0173088, 2017.
Article
en En
| MEDLINE
| ID: mdl-28257450
ABSTRACT
Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent to prevent or treat allotransplant rejection. The aim of the present study was to investigate the effect of low dose ATG treatment exclusively on T cells using a humanized BALB/c human CD3Æ transgenic mouse model expressing both human and murine T cell receptors (TCR). Mice received a single intravenous (i.v.) injection of ATG. Blood and peripheral lymphoid organs were obtained after different time points. We found a significant T cell depletion in this mouse model. In addition, regulatory T cells (Tregs) proved to be less sensitive to depletion than the rest of T cells and the Tregnon-Treg ratio was therefore increased. Finally, we also investigated the effect of ATG in a heterotopic allogenic murine model of heart transplantation. Survival and transplant function were significantly prolonged in ATG-treated mice. In conclusion, we showed (a) an immunosuppressive effect of ATG in this humanized mouse model which is exclusively mediated by reactivity against human CD3Æ; (b) provided evidence for a relative resistance of Tregs against this regimen; and
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trasplante de Corazón
/
Complejo CD3
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Linfocitos T Reguladores
/
Rechazo de Injerto
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Inmunosupresores
/
Suero Antilinfocítico
Límite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Austria