4-1BB (CD137) signals depend upon CD28 signals in alloimmune responses
Experimental & Molecular Medicine
;
: 606-615, 2006.
Article
in English
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Transplantation, Homologous
/
Cytotoxicity Tests, Immunologic
/
Signal Transduction
/
Heart Transplantation
/
Mice, Knockout
/
CD28 Antigens
/
4-1BB Ligand
/
Graft Survival
/
Isoantigens
/
Antibodies
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2006
Type:
Article
Similar
MEDLINE
...
LILACS
LIS