The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade.

The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade. Research Abstract Details 

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The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade. Abstract Text:

Emily A Rowell,Liqing Wang,Wayne W Hancock,Andrew D Wells,

The cyclin-dependent kinase (CDK) inhibitor p27kip1 is an important negative regulator of the cell cycle that sets a threshold for mitogenic signals in T lymphocytes, and is required for T cell anergy in vitro. To determine whether p27(kip1) is required for tolerance in vivo, we performed cardiac allograft transplantation under conditions of combined CD28/CD40L costimulatory blockade. Although this treatment induced long-term allograft survival in wild-type recipients, costimulatory blockade was no longer sufficient to induce tolerance in mice lacking p27kip1. Rejected allografts from p27kip1-/- mice contained more CD4+ T lymphocytes and exhibited more tissue damage than allografts from tolerant, wild-type mice. Infiltrating p27kip1-deficient T cells, but not wild-type T cells, exhibited nuclear expression of cyclins E and A, indicating uncontrolled T cell cycle progression in the graft. The failure of tolerance in p27kip1-/- mice was also accompanied by markedly increased numbers of allospecific, IFN-gamma-producing cells in the periphery, and occurred despite apparently normal regulatory T cell activity. These data demonstrate that the CDK inhibitor p27kip1 enforces the costimulatory requirement for the expansion and differentiation of alloimmune effector T lymphocytes in vivo, and point to CDKs as novel targets for immunosuppressive or tolerance-inducing therapies.

The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade. Publishing Authors By Initials

EA Rowell,L Wang,WW Hancock,AD Wells,

For similar biological phenomena, cell phenomena, and immunity: immunity: immune tolerance: transplantation tolerance research abstracts see: biological phenomena, cell phenomena, and immunity: immunity: immune tolerance: transplantation tolerance research

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The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 177

Page Numbers: 5169-76

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Oct

YEAR: 2006

The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade. Keywords Mesh Terms:

KEYWORDS: Transplantation Tolerance

MESH TERMS: immunology

Chemical & Substance for Abstract: The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade. Information

Substance Name: Cyclin-Dependent Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade.

AFFILIATION: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Country: United States

AGENCY: United States NIAMS

GRANT: T32-AR007442-18

ACRONYM: AR

MEDLINETA: J Immunol

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