Differential expression of T-cell growth factors in rejecting murine islet and human renal allografts: conspicuous absence of interleukin (IL)-9 despite expression of IL-2, IL-4, IL-7, and IL-15.
BACKGROUND
Interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15, all T-cell growth factors (TCGFs), utilize the common IL-2 receptor gammac chain as a critical signaling component in their receptor complexes. We have bred IL-2-/- and IL-4-/- double knockout (DKO) mice and showed vigorous islet allograft rejection by DKO hosts. The identity of TCGFs that support the IL-2- and IL-4-independent allograft rejection is unclear.


METHODS
We analyzed IL-9 gene expression in rejecting islet allografts in wild-type and in DKO mice, as well as in human renal transplant biopsy specimens, by reverse transcriptase polymerase chain reaction and compared the expression of IL-9 with that of other TCGFs.


RESULTS
IL-9 gene expression was not detected in rejecting murine islet allografts in either wild-type or DKO recipient mice despite robust expression of other TCGFs, including IL-7 and IL-15. IL-9 transcripts were also not expressed in any of the human renal transplant biopsies obtained 4 to 251 days after transplantation, regardless of the presence or absence of histological evidence of rejection. Despite expression of IL-9 by DKO splenic cells upon in vitro mitogenic stimulation, IL-9 alone was unable to stimulate the proliferation of concanavalin A-activated splenic leukocytes harvested from DKO mice.


CONCLUSIONS
IL-9 is conspicuously absent despite vigorous expression of IL-2, IL-4, IL-7, and IL-15 genes during acute allograft rejection.
Li
X C
XC
Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Children's Hospital, Boston, Massachusetts 02215, USA.
Schachter
A D
AD
Zand
M S
MS
Li
Y
Y
Zheng
X X
XX
Harmon
W E
WE
Strom
T B
TB
D000818:Animals; D006084:Graft Rejection; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D015851:Interleukin-7 / Q000235:genetics; D016906:Interleukin-9 / Q000235:genetics; D016381:Islets of Langerhans Transplantation; D016030:Kidney Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D014184:Transplantation, Homologous
D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D016906:Interleukin-9; D012333:RNA, Messenger; D015847:Interleukin-4