Induction of suppressive allogeneic regulatory T cells via rabbit antithymocyte polyclonal globulin during homeostatic proliferation in rat kidney transplantation.
Transpl Int
; 28(1): 108-19, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-25208307
ABSTRACT
Experimental studies have shown that rabbit antithymocyte polyclonal globulin (ATG) can expand human CD4+CD25++Foxp3+ cells (Tregs). We investigated the major biological effects of a self-manufactured rabbit polyclonal anti-rat thymoglobulin (rATG) in vitro, as well as its effects on different peripheral T-cell subsets. Moreover, we evaluated the allogeneic suppressive capacity of rATG-induced Tregs in an experimental rat renal transplant model. Our results show that rATG has the capacity to induce apoptosis in T lymphocyte lymphocytes as a primary mechanism of T-cell depletion. Our in vivo studies demonstrated a rapid but transient cellular depletion of the main T cell subsets, directly proportional to the rATG dose used, but not of the effector memory T cells, which required significantly higher rATG doses. After rATG administration, we observed a significant proliferation of Tregs in the peripheral blood of transplanted rats, leading to an increase in the Treg/T effector ratio. Importantly, rATG-induced Tregs displayed a strong donor-specific suppressive capacity when assessed in an antigen-specific allogeneic co-culture. All of these results were associated with better renal graft function in rats that received rATG. Our study shows that rATG has the biological capacity immunomodulatory to promote a regulatory alloimmune milieu during post-transplant homeostatic proliferation.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trasplante de Riñón
/
Linfocitos T Reguladores
/
Timocitos
/
Suero Antilinfocítico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Transpl Int
Asunto de la revista:
TRANSPLANTE
Año:
2015
Tipo del documento:
Article
País de afiliación:
España