Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice.

Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice. Research Abstract Details 

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Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice. Abstract Text:

Tatsuhiko Asai,Beom K Choi,Patrick M Kwon,Won Y Kim,Jung D Kim,Dass S Vinay,Bryan M Gebhardt,Byoung S Kwon,

To explore the roles of 4-1BB (CD137) and CD28 in corneal transplantation, we examined the effect of 4-1BB/4-1BB ligand (4-1BBL) and/or CD28/CD80/CD86 blockade on corneal allograft survival in mice. Allogeneic corneal transplantation was performed between two strains of wild-type (WT) mice, BALB/c and C57BL/6 (B6), and between BALB/c and B6 WT donors and various gene knockout (KO) recipients. Some of the WT graft recipients were treated intraperitoneally with agonistic anti-4-1BB or blocking anti-4-1BBL monoclonal antibody (mAb) on days 0, 2, 4 and 6 after transplantation. Transplanted eyes were observed over a 13-week period. Allogeneic grafts in control WT B6 and BALB/c mice treated with rat immunoglobulin G showed median survival times (MST) of 12 and 14 days, respectively. Allogeneic grafts in B6 WT recipients treated with anti-4-1BB mAb showed accelerated rejection, with an MST of 8 days. In contrast, allogeneic grafts in BALB/c 4-1BB/CD28 KO and B6 CD80/CD86 KO recipients had significantly prolonged graft survival times (MST, 52.5 days and 36 days, respectively). Treatment of WT recipients with anti-4-1BB mAb resulted in enhanced cellular proliferation in the mixed lymphocyte reaction and increased the numbers of CD4(+) CD8(+) T cells, and macrophages in the grafts, which correlated with decreased graft survival time, whereas transplant recipients with costimulatory receptor deletion showed longer graft survival times. These results suggest that the absence of receptors for the 4-1BB/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival, whereas triggering 4-1BB with an agonistic mAb enhances the rejection of corneal allografts.

Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice. Publishing Authors By Initials

T Asai,BK Choi,PM Kwon,WY Kim,JD Kim,DS Vinay,BM Gebhardt,BS Kwon,

For similar nucleic acids, nucleotides, and nucleosides: nucleic acids: rna: rna, messenger research abstracts see: nucleic acids, nucleotides, and nucleosides: nucleic acids: rna: rna, messenger research

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Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Immunology

VOLUME: 121

Page Numbers: 349-58

Journal Abbreviation: Immunology

ISSN: 0019-2805

DAY: 22

MONTH: 03

YEAR: 2007

Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice. Information

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LANGUAGE: eng

NlmUniqueID: 374672

Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice. Keywords Mesh Terms:

KEYWORDS: RNA, Messenger

MESH TERMS: genetics

Chemical & Substance for Abstract: Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice. Information

Substance Name: RNA, Messenger

Registry Number: 0

Grant and Affiliation Information for Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice.

AFFILIATION: LSU Eye Center, LSU Health Sciences Center School of Medicine, New Orleans, LA, USA.

Country: England

AGENCY: United States NEI

GRANT: R01EY013325

ACRONYM: EY

MEDLINETA: Immunology

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