Acute allograft rejection in human liver transplant recipients is associated with signaling through toll-like receptor 4.
J Gastroenterol Hepatol
; 26(1): 155-63, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-21175809
ABSTRACT
BACKGROUND AND AIMS:
Toll-like receptor (TLR) signaling is a crucial step in initiating adaptive immune responses. In addition to recognizing endotoxin, TLR4 also recognizes endogenous ligands ('damage-associated structures'), which are released into the circulation in the peri-transplantation period. TLR2 to a lesser extent also recognizes these endogenous ligands. Multiple studies involving solid organ transplants demonstrate a clear association between TLR4 and allograft rejection. In the present study we assessed whether an association exists between TLR4 and TLR2-dependent responses and acute liver allograft rejection.METHODS:
The sample included 26 liver transplant recipients. Blood was taken pre-transplant and at multiple points over the first 14 days post-transplant. Monocytes were stimulated with TLR4 and TLR2 ligands, lipopolysaccharide and Pam-3-Cys, respectively. Monocyte TLR expression was determined using flow cytometry; enzyme-linked immunosorbent assays measured tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production.RESULTS:
Nine (34.6%) patients experienced rejection. No differences existed in age, sex, disease or immunosuppression between rejectors and non-rejectors. Baseline TLR4 expression was significantly higher in rejectors (1.36 vs 1.02, P=0.01). There was no difference in TLR2 expression. In rejectors, baseline TLR4- and TLR2-dependent production of TNF-α and IL-6 was also significantly increased. Post-transplant, the two groups differed with regard to TLR4-dependent TNF-α production, with rejectors demonstrating progressive downregulation over the first week.CONCLUSIONS:
Prior to liver transplantation, patients who subsequently experience rejection demonstrate robust TLR4-dependent immune responses, which are not seen in those who do not reject. This supports the theory that damage-associated structures signaling through TLR4 may be responsible for the early activation of alloimmune T-cells, favoring allograft rejection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Monócitos
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Transdução de Sinais
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Transplante de Fígado
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Receptor 4 Toll-Like
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Rejeição de Enxerto
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Imunidade Inata
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
País como assunto:
Oceania
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article