Graft produced interleukin-6 functions as a danger signal and promotes rejection after transplantation.

Graft produced interleukin-6 functions as a danger signal and promotes rejection after transplantation. Research Abstract Details 

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Graft produced interleukin-6 functions as a danger signal and promotes rejection after transplantation. Abstract Text:

Yurong Liang,Kenneth Christopher,Patricia W Finn,Yolonda L Colson,David L Perkins,

BACKGROUND: Interleukin (IL)-6 is a pleiotropic cytokine that functions in both the innate and adaptive immune responses. However, the role of IL-6 in allograft rejection remains poorly understood. METHODS: In this study, we demonstrate a critical role for graft-produced IL-6 in allograft rejection in a murine model of cardiac allograft transplantation. RESULTS: The results show that IL-6-deficient grafts transplanted into allogeneic wild-type recipients have significantly prolonged survival, approximately three times the survival time of wild-type controls. In contrast, allogeneic cardiac transplants into IL-6-deficient recipients do not have prolonged graft survival, indicating that donor graft cells are the relevant source of IL-6. Our investigation of potential mechanisms shows that graft-produced IL-6 promotes the activation of peripheral CD4 and CD8 T cells. Furthermore, we show that IL-6 deficiency prolongs graft survival only in the presence of CD25+ T cells that have a phenotype consistent with regulatory T cells. Interestingly, IL-6 production by the graft is triggered by antigen-independent innate immune mechanisms. CONCLUSIONS: Thus, our results suggest the paradigm that graft rejection versus tolerance is determined by a balance between the activation of effector T cells versus immune suppression by regulatory T cells, and that after transplantation, IL-6 functions as a systemic danger signal that overcomes constitutive immune suppression mediated by regulatory T cells and promotes the activation of effector T cells.

Graft produced interleukin-6 functions as a danger signal and promotes rejection after transplantation. Publishing Authors By Initials

Y Liang,K Christopher,PW Finn,YL Colson,DL Perkins,

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Graft produced interleukin-6 functions as a danger signal and promotes rejection after transplantation. Journal Published:

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

Journal: Transplantation

VOLUME: 84

Page Numbers: 771-7

Journal Abbreviation: Transplantation

ISSN: 0041-1337

DAY: 27

MONTH: Sep

YEAR: 2007

Graft produced interleukin-6 functions as a danger signal and promotes rejection after transplantation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 132144

Graft produced interleukin-6 functions as a danger signal and promotes rejection after transplantation. Keywords Mesh Terms:

KEYWORDS: Transplants

MESH TERMS: metabolism

Chemical & Substance for Abstract: Graft produced interleukin-6 functions as a danger signal and promotes rejection after transplantation. Information

Substance Name: Interleukin-6

Registry Number: 0

Grant and Affiliation Information for Graft produced interleukin-6 functions as a danger signal and promotes rejection after transplantation.

AFFILIATION: Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.

Country: United States

AGENCY: United States NIAID

GRANT: R01 AI44085

ACRONYM: AI

MEDLINETA: Transplantation

REFSOURCE: Transplantation. 2007 Nov 27;84(10):1375

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