Interleukin-9 promotes eosinophilic rejection of mouse heart allografts.
BACKGROUND
Eosinophils participate in allograft rejection when donor-reactive helper T lymphocytes are T-helper type 2 (Th2)-biased. Whereas the involvement of interleukin (IL)-4 and IL-5 in these forms of rejection is well established, the role of IL-9, another Th2-type cytokine promoting eosinophilia, has not been determined.


METHODS
We first used real-time polymerase chain reaction to quantify IL-9 mRNA in rejected allografts in a mouse model of fully mismatched heart transplantation in which recipients were devoid of CD8 T cells and developed a Th2 alloimmune response. We then compared allograft survival in wild-type versus IL-9-deficient mice depleted of CD8 T cells. Finally, we compared the fate of major histocompatibility complex class II-mismatched cardiac transplants from wild-type versus IL-9 transgenic donors to determine the influence of IL-9 overexpression within the graft.


RESULTS
The Th2 alloimmune response in CD8-deficient mice was associated with the accumulation of IL-9 mRNA in the rejected graft. In IL-9-deficient recipients depleted of CD8 T cells, eosinophil infiltration of heart allografts did not develop, but rejection still occurred. In the major histocompatibility complex class II disparate model, heart allografts from IL-9 transgenic donors were acutely rejected, whereas grafts from wild-type donors did not develop rejection. Acute rejection of IL-9 transgenic hearts was associated with massive eosinophil infiltration and prevented by neutralization of either IL-4 or IL-5.


CONCLUSIONS
IL-9 is critically involved in heart transplant eosinophilia in conjunction with IL-4 and IL-5.
Poulin
Lionel F
LF
The Laboratory of Experimental Immunology, Université Libre de Bruxelles, 808 route de Lennik, 1070 Brussels, Belgium.
Richard
Mélisande
M
Le Moine
Alain
A
Kiss
Robert
R
McKenzie
Andrew N
AN
Goldman
Michel
M
Renauld
Jean-Christophe
JC
Van Snick
Jacques
J
Braun
Michel Y
MY
D000818:Animals; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000502:physiology*; D006084:Graft Rejection / Q000503:physiopathology*; D016027:Heart Transplantation; D015847:Interleukin-4 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D016906:Interleukin-9 / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018418:Th2 Cells / Q000276:immunology; D014184:Transplantation, Homologous
D015848:Interleukin-5; D016906:Interleukin-9; D012333:RNA, Messenger; D015847:Interleukin-4