Hyperexpression of Foxp3 and IDO during acute rejection of islet allografts.

Abstract:

BACKGROUND:We investigated the hypothesis that Foxp3+ cells are an integral component of antiallograft immunity but are dominated by pathogenic effectors. METHODS:Wild-type H-2b C57BL/6 (B6) mice or B6 mice with a targeted disruption of c-Rel gene (c-Rel-/-) were used as recipients of islet grafts from allogeneic DBA/2 (H-2d) mice or syngeneic B6 mice. We developed kinetic quantitative polymerase chain reaction assays and measured intragraft expression of mRNA for Foxp3, IDO, cytolytic molecules, proinflammatory cytokines, and chemokines/receptors. RESULTS:Intraislet levels of mRNA for Foxp3, IDO, CD3, CD25, tumor necrosis factor-alpha, RANTES, IP-10, and CXCR3 were highest in DBA/2 islet allografts from WT B6 recipients compared to DBA/2 islet allografts from c-Rel-/- B6 recipients or syngeneic B6 islet grafts from WT B6 mice. The ratio of granzyme B or IFN-gamma to Foxp3 was higher with the DBA/2 islet allografts from the WT B6 recipients compared to DBA/2 islet allografts from c-Rel-/- B6 recipients or B6 islet grafts from WT B6 recipients. CONCLUSIONS:Foxp3+ cells are an integral component of acute rejection of allografts but may be dominated by pathogenic effectors.

journal_name

Transplantation

journal_title

Transplantation

authors

Yang H,Ding R,Sharma VK,Hilaire FS,Lagman M,Li B,Thomas DA,Luo X,Song P,Stauffer C,August P,Suthanthiran M

doi

10.1097/01.tp.0000263991.74052.46

subject

Has Abstract

pub_date

2007-06-27 00:00:00

pages

1643-7

issue

12

eissn

0041-1337

issn

1534-6080

pii

00007890-200706270-00020

journal_volume

83

pub_type

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