Hyperexpression of Foxp3 and IDO during acute rejection of islet allografts.
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.
Yang
Hua
H
Division of Nephrology and Hypertension, Department of Medicine, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY 10021, USA.
Ding
Ruchuang
R
Sharma
Vijay K
VK
Hilaire
Fludd Saint
FS
Lagman
Milagros
M
Li
Baogui
B
Thomas
Dolca A
DA
Thomas
Dolea A
DA
Luo
Xunrong
X
Song
Ping
P
Stauffer
Craig
C
August
Phyllis
P
Suthanthiran
Manikkam
M
D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006084:Graft Rejection / Q000473:pathology*; D053804:Granzymes / Q000235:genetics; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D016381:Islets of Langerhans Transplantation / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D020569:Proto-Oncogene Proteins c-rel / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D053804:Granzymes