TOLERANCE INDUCTION TO CULTURED ISLET ALLOGRAFTS .1. CHARACTERIZATIONOF THE TOLERANT STATE

The immunogenicity of murine pancreatic islets can be reduced by cultu re in 95% O-2 prior to transplantation. Such cultured tissue can rever se diabetes indefinitely in nonimmunosuppressed, allogeneic recipients . Although the cultured graft does not trigger a rejection response, t he graft retains recognizable alloantigens in that the graft is acutel y rejected when the host is immunized with donor-type antigen-presenti ng cells. However, over time the recipients bearing cultured islet all ografts become increasingly resistant to rejecting the established gra ft following APC challenge. Data show that this process of graft ''sta bilization'' is a function of time postgrafting and initial graft mass . Graft stabilization is not due to a change in the vulnerability of t he graft to immune recognition-that is, stabilization cannot be accoun ted for by the spontaneous adaptation of the long-term graft. Rather, graft stabilization is associated with a change in host reactivity (to lerance induction). This conclusion is based on the findings that (I) recipients of long-term established grafts (>120 days) resist rejectio n of both the primary and secondary donor-type grafts, and (2) donor-s pecific tolerance can be transferred to severe-combined-immune-deficie nt (scid) recipient mice.