ALLOGENEIC AND XENOGENEIC ISLETS ARE REJECTED BY DIFFERENT AND SPECIFIC MECHANISMS - A STUDY IN RODENTS USING A MIXED ALLOGENEIC-XENOGENEICISLET TRANSPLANTATION MODEL
L. Wennberg et al., ALLOGENEIC AND XENOGENEIC ISLETS ARE REJECTED BY DIFFERENT AND SPECIFIC MECHANISMS - A STUDY IN RODENTS USING A MIXED ALLOGENEIC-XENOGENEICISLET TRANSPLANTATION MODEL, Xenotransplantation, 4(4), 1997, pp. 228-234
Citations number
24
Categorie Soggetti
Transplantation,"Medicine, Research & Experimental
Indirect evidence suggests that islet allo-and xeno-graft rejections a
re two qualitatively, and not simply quantitatively, different process
es. This, however, has never been clearly shown and a direct in vivo c
omparison of cell-mediated allo-and xeno-graft rejections has never be
en made, Therefore, Lewis rats were transplanted with either Wistar-Fu
rth rat islets or fetal porcine islet-like cell clusters (ICC) under t
he kidney capsule. Other Lewis rats were transplanted with Wistar-Furt
h rat islets and fetal porcine ICC, which were mixed together into one
single graft. Animals were left untreated or were treated with cyclos
porin A (CyA, 20 mg/kg b.w., p.,o.,) daily. Twelve days following tran
splantation, islet allo-and xeno-graft survival was evaluated morpholo
gically and any cellular infiltration into the grafts was characterize
d immunohistochemically. In untreated animals, both allogeneic and xen
ogeneic islets were destroyed by massive cellullar infiltration. The m
ain infiltrating cells in islet allograft rejection were TCR alpha/bet
a-positive T-cells. In contrast, the main infiltrating cells in islet
xenograft rejection were EDI-and ED2-positive macrophages. In islet xe
nograft rejection, only a few T-cells were: found. In islet allografts
removed from rats treated with CyA, many morphologically intact rat i
slets were found. Only a few infiltrating cells were detected and thes
e were both ED1-positive macrophages and TCR alpha/beta-positive T-cel
ls. In CyA-treated rats transplanted with porcine ICC, we noted a mass
ive infiltration with ED1- and ED2-positive macrophages and TCR alpha/
beta-positive T-cells, similar to that observed in untreated animals.
Na endocrine cells were present. In mixed allogeneic-xenogeneic islet
grafts transplanted into CyA-treated rats, many morphologically intact
rat islets were found, as evidenced by positive staining for rat MHC
class I. However, no porcine ICC remained, The xenogeneic islets in th
ese mixed grafts were destroyed, by massive cellular infiltration, sim
ilar to that observed after transplantation of xenogeneic islets alone
. Obviously, the xenogeneic islets in these mixed grafts were rejected
by a cell-mediated process qualitatively different from that of cell-
mediated allograft rejection.