K. Hayamizu et al., Comparison of chimeric and non-chimeric tolerance using posttransplant total lymphoid irradiation - Cytokine expression and chronic rejection, TRANSPLANT, 68(7), 1999, pp. 1036-1044
Background. Previous studies showed that an intravenous infusion of donor b
lood cells facilitates tolerance to ACI heart allografts in Lewis rat hosts
given posttransplant total lymphoid irradiation (TLI) and anti-thymocyte g
lobulin (ATG), The object of the current study was to compare tolerance ind
uction using donor cells that do or do not induce chimerism,
Methods. Normal peripheral blood mononuclear cells (PBMC), granulocyte colo
ny-stimulating factor (G-CSF)-mobilized PBMC, and bone marrow (BM) cells fr
om ACI donors were tested for their capacity to prolong ACI heart allograft
survival in Lewis hosts, Chimerism, anti-donor cell reactivity, and cytoki
ne gene expression in grafts were determined.
Results. Intravenous injections of equal numbers of all three donor cells m
arkedly prolonged graft survival (median: >164 to >175 days) as compared to
uninjected controls (median: 53 days). Chimerism among T and B cells in th
e blood was determined by immunofluorescent staining in hosts bearing long-
term (>150 days) grafts. Although no chimerism was detected in hosts given
normal or G-CSF-mobilized PBMC, chimerism was detected at variable levels i
n all hosts given BM cells. Vigorous anti-donor reactivity in the mixed leu
kocyte reaction was present only in non-chimeric hosts, Long-term grafts fr
om hosts given normal ACI PBMC developed chronic rejection, but those from
hosts given ACI BM cells did not. The latter hosts showed the lowest levels
of intragraft cytokine mRNA.
Conclusions. Chimeric tolerance is more robust than non-chimeric tolerance
in the model of posttransplant TLI, ATG, and donor cell infusion, and is as
sociated with less chronic rejection.