4-1BB (CD137) signals depend upon CD28 signals in alloimmune responses.
- Author:
Eun A LEE
1
;
Jeong Eun KIM
;
Jae Hee SEO
;
Byoung Se KWON
;
Seok Hyun NAM
;
Byungsuk KWON
;
Hong Rae CHO
Author Information
1. The Immunomodulation Research Center, University of Ulsan, Ulsan 680-742, Korea. hrcho@uuh.ulsan.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
antibody formation;
antigens;
CD28;
CD137 antigen;
graft rejection;
mice;
knockout
- MeSH:
Transplantation, Homologous/immunology;
Signal Transduction/*immunology;
Mice, Knockout;
Mice;
Isoantigens/immunology;
Heart Transplantation/immunology;
Graft Survival/immunology;
Cytotoxicity Tests, Immunologic;
Antigens, CD28/genetics/*immunology/metabolism;
Antibodies/immunology;
Animals;
4-1BB Ligand/deficiency/genetics/*immunology/metabolism
- From:Experimental & Molecular Medicine
2006;38(6):606-615
- CountryRepublic of Korea
- Language:English
-
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.
