4-1BB (CD137) signals depend upon CD28 signals in alloimmune responses
Experimental & Molecular Medicine
;
: 606-615, 2006.
Article
Dans Anglais
| WPRIM
| ID: wpr-106425
ABSTRACT
Our previous study has demonstrated that there is a significant delay of Balb/c cardiac allograft rejection in the C57BL/6 4-1BB-deficient knockout recipient. In this study, we examined the effect of combined blockade of the 4-1BB and CD28 costimulatory pathways on cardiac allograft rejection in the C57BL/6-->Balb/c model. A long-term cardiac allograft survival was induced in CD28/4-1BB- deficient mice (>100 days survival in 3 of 4 mice), which was comparable with CD28-deficient mice (>100 days survival in 2 of 5 mice; P<0.2026). There was no long-term cardiac allograft survival in either wild-type (WT) or 4-1BB-deficient mice, even though 4-1BB-deficient recipients showed a significant delay of cardiac allograft rejection than WT mice. An in vitro mixed leukocyte reaction (MLR) assay showed that 4-1BB-deficient and WT mouse T cells had a similar responsiveness to allostimulation, whereas CD28- and CD28/4-1BB-deficient mouse T cells had a defective responsiveness to allostimulation. Furthermore, 4-1BB-deficient mice showed a similar CTL but an elevated Ab response against alloantigens as compared to WT mice, and the alloimmune responses of 4-1BB-deficient mice were abrogated in the CD28-deficient background. Overall, these results indicate that the CD28 costimulatory pathway plays a major role in the alloimmune response and that 4-1BB signals are dependent upon CD28 signals.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Transplantation homologue
/
Tests de cytotoxicité immunologique
/
Transduction du signal
/
Transplantation cardiaque
/
Souris knockout
/
Antigène CD28
/
Ligand de 4-1BB
/
Survie du greffon
/
Isoantigènes
/
Anticorps
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
langue:
Anglais
Texte intégral:
Experimental & Molecular Medicine
Année:
2006
Type:
Article
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