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Transplant Research Division, The Toronto Hospital, Toronto, Canada
We have established that, in mice receiving donor-specific
immunization by the portal vein, the increased graft survival seen is
associated with the increased expression of a molecule (OX-2) on a
subpopulation of dendritic cells (DC), and polarization of cytokine
production to type 2 cytokines on Ag-specific restimulation of cells
from these mice. Furthermore, infusion of a mAb to OX-2 blocks both the
increased graft survival and the altered cytokine production seen. We
have constructed an immunoadhesin in which the extracellular domain of
OX-2 is linked to the murine IgG2a Fc region, and we have expressed
this molecule (OX-2:Fc) in a eukaryotic (baculovirus) expression
system. Incubation of lymphocytes with 50 ng/ml OX-2:Fc inhibits a
primary mixed lymphocyte reaction in vitro, as assayed by proliferation
and induction of cytotoxic T cells, and also alters cytokine production
with decreased IL-2 (IFN-
) production and increased IL-4 (IL-10)
production. Similarly, in vivo infusion of OX-2:Fc promotes increased
allo- and xenograft (both skin and renal grafts) survival and decreases
the Ab response to sheep erythrocytes. Our data suggest this molecule
might have clinical importance in allo- and
xenotransplantation.
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