Background. Acute rejection of allografts remains a significant problem in
clinical transplantation, and the fundamental mechanism underlying this rej
ection are as yet only poorly elucidated. Recently, DNA microarrays have co
me into use for the study of gene expression profiles, and we have taken ad
vantage of this new technology to investigate acute rejection. We compared
mRNA profiles in murine cardiac allografts with isografts using DNA microar
rays with probe sets corresponding to more than 11,000 mice genes.
Methods. We screened for gene expression changes in murine cardiac allograf
ts between fully incompatible mice strains (BALB/c H2(d) to C3H/He H2(k)) u
sing a DNA microarray. The heart was heterotopically transplanted. Allograf
ts (BALB/c to C3H/He) were removed on days 1, 3, and 5. As a control, isogr
afts (C3H/He to C3H/He) harvested on days 1, 3, and 5 and native hearts of
both strain mice (C3H/He and BALB/c) were obtained.
Results. On day 5, interferon-gamma (IFN-gamma) and many IFN-gamma -inducib
le genes were profoundly induced in the allograft relative to isograft, Mon
okine induced by IFN-gamma was most profoundly induced followed by inducibl
y expressed GTPase and Lmp-2. IFN-gamma was also profoundly induced. The in
duction was detectable from day 3. In contrast, genes regulated by other cy
tokines exhibited only modest changes.
Conclusion. IFN-gamma -inducible genes are specifically up-regulated in mur
ine cardiac allografts, suggesting that signaling mediated by IFN-gamma may
play an important role in the late phase of acute rejection in vivo.