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Blockade of 4-1BB (CD137)/4-1BB ligand interactions increases allograft survival.
Transpl Int. 2004 Aug; 17(7):351-61.TI

Abstract

We investigated the role of 4-1BB, a T cell co-stimulatory molecule, in alloimmune responses. In vivo mixed lymphocyte reactions showed that 4-1BB was preferentially expressed on actively dividing CD4(+) and CD8(+) T cells. Furthermore, following alloantigen challenge, the draining lymph nodes contained subpopulations of 4-1BB-expressing CD4(+) and CD8(+) T cells. 4-1BB-deficient C57BL/6 mice showed a delayed rejection of cardiac transplants mismatched for the major histocompatibility complex. Longer transplant survival was induced by blockade of 4-1BB/4-1BB ligand (4-1BBL) interactions using an anti-4-1BBL monoclonal antibody. Histological analysis showed that prolonged transplant survival in the 4-1BB-deficient and anti-4-1BBL-treated mice correlated with reduced lymphocytic infiltration and vasculitis in the donor heart tissue. Taken together, our data suggest that blockade of 4-1BB/4-1BBL interactions inhibited the expansion of alloreactive T cells and reduced CTL activity against host alloantigen, which in turn resulted in the prolongation of allograft survival. Blockade of the 4-1BB co-stimulatory pathway may be useful for preventing allograft rejection.

Links

Publisher Full Text
link.springer.com
doi.org

Authors+Show Affiliations

Cho HR
Immunomodulation Research Center, University of Ulsan, 682-714, Ulsan, Korea.
Kwon B
No affiliation info available
Yagita H
No affiliation info available
La S
No affiliation info available
Lee EA
No affiliation info available
Kim JE
No affiliation info available
Akiba H
No affiliation info available
Kim J
No affiliation info available
Suh JH
No affiliation info available
Vinay DS
No affiliation info available
Ju SA
No affiliation info available
Kim BS
No affiliation info available
Mittler RS
No affiliation info available
Okumura K
No affiliation info available
Kwon BS
No affiliation info available

MeSH

4-1BB LigandAnimalsAntibodies, MonoclonalAntigens, CDCell DivisionDendritic CellsFemaleGraft RejectionGraft SurvivalHeart TransplantationIsoantigensLymphocyte Culture Test, MixedMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred DBAMice, Mutant StrainsReceptors, Nerve Growth FactorReceptors, Tumor Necrosis FactorSignal TransductionSkin TransplantationT-LymphocytesTransplantation, HomologousTumor Necrosis Factor Receptor Superfamily, Member 9Tumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15349720

Citation

Cho, H R., et al. "Blockade of 4-1BB (CD137)/4-1BB Ligand Interactions Increases Allograft Survival." Transplant International : Official Journal of the European Society for Organ Transplantation, vol. 17, no. 7, 2004, pp. 351-61.
Cho HR, Kwon B, Yagita H, et al. Blockade of 4-1BB (CD137)/4-1BB ligand interactions increases allograft survival. Transpl Int. 2004;17(7):351-61.
Cho, H. R., Kwon, B., Yagita, H., La, S., Lee, E. A., Kim, J. E., Akiba, H., Kim, J., Suh, J. H., Vinay, D. S., Ju, S. A., Kim, B. S., Mittler, R. S., Okumura, K., & Kwon, B. S. (2004). Blockade of 4-1BB (CD137)/4-1BB ligand interactions increases allograft survival. Transplant International : Official Journal of the European Society for Organ Transplantation, 17(7), 351-61.
Cho HR, et al. Blockade of 4-1BB (CD137)/4-1BB Ligand Interactions Increases Allograft Survival. Transpl Int. 2004;17(7):351-61. PubMed PMID: 15349720.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockade of 4-1BB (CD137)/4-1BB ligand interactions increases allograft survival. AU - Cho,H R, AU - Kwon,B, AU - Yagita,H, AU - La,S, AU - Lee,E A, AU - Kim,J-E, AU - Akiba,H, AU - Kim,J, AU - Suh,J-H, AU - Vinay,D S, AU - Ju,S-A, AU - Kim,B-S, AU - Mittler,R S, AU - Okumura,K, AU - Kwon,B S, Y1 - 2004/07/31/ PY - 2003/06/05/received PY - 2004/02/12/revised PY - 2004/03/05/accepted PY - 2004/9/7/pubmed PY - 2005/2/19/medline PY - 2004/9/7/entrez SP - 351 EP - 61 JF - Transplant international : official journal of the European Society for Organ Transplantation JO - Transpl Int VL - 17 IS - 7 N2 - We investigated the role of 4-1BB, a T cell co-stimulatory molecule, in alloimmune responses. In vivo mixed lymphocyte reactions showed that 4-1BB was preferentially expressed on actively dividing CD4(+) and CD8(+) T cells. Furthermore, following alloantigen challenge, the draining lymph nodes contained subpopulations of 4-1BB-expressing CD4(+) and CD8(+) T cells. 4-1BB-deficient C57BL/6 mice showed a delayed rejection of cardiac transplants mismatched for the major histocompatibility complex. Longer transplant survival was induced by blockade of 4-1BB/4-1BB ligand (4-1BBL) interactions using an anti-4-1BBL monoclonal antibody. Histological analysis showed that prolonged transplant survival in the 4-1BB-deficient and anti-4-1BBL-treated mice correlated with reduced lymphocytic infiltration and vasculitis in the donor heart tissue. Taken together, our data suggest that blockade of 4-1BB/4-1BBL interactions inhibited the expansion of alloreactive T cells and reduced CTL activity against host alloantigen, which in turn resulted in the prolongation of allograft survival. Blockade of the 4-1BB co-stimulatory pathway may be useful for preventing allograft rejection. SN - 0934-0874 UR - https://www.unboundmedicine.com/medline/citation/15349720/Blockade_of_4_1BB__CD137_/4_1BB_ligand_interactions_increases_allograft_survival_ L2 - http://link.springer.com/article/10.1007/s00147-004-0726-3 DB - PRIME DP - Unbound Medicine ER -