Jp. Smith et al., ASSESSMENT OF DONOR BONE-MARROW CELL-DERIVED CHIMERISM IN TRANSPLANTATION TOLERANCE USING TRANSGENIC MICE, Transplantation, 58(3), 1994, pp. 324-329
Allospecific skin graft prolongation can be induced in mice using anti
thymocyte globulin and allospecific donor bone marrow cells (DBMC). Th
is enhancement may be due to the persistence of chimeric cells of dono
r origin in the host. In this study, we systematically investigated DB
MC-derived chimerism in various lymphoid and nonlymphoid tissues over
time. To do this, transgenic mice were used as a source of DBMC to cle
arly distinguish chimerism due only to the injected DBMC. Chimerism in
various tissues was assessed at several times points after DBMC infus
ion by polymerase chain reaction amplification of tissue DNA using tra
nsgene specific primers. A cDNA probe specific for the transgene was u
sed to demonstrate DBMC-derived chimerism in polymerase chain reaction
products by the method of Southern. Although chimerism was initially
detectable in most tissues tested 1 day after DBMC infusion, the prese
nce of chimeric cells generally diminished over time. At 4 weeks or lo
nger, chimerism was consistently confined to recipient skin. Furthermo
re, the chimeric cells in recipient skin persisted even after the allo
graft was rejected. In contrast to chimerism in recipient skin, chimer
ism became undetectable in donor skin as early as 2 weeks after DBMC i
nfusion. The loss of chimerism in donor skin showed a temporal correla
tion with a reduction of chimerism in host bone marrow and lymphoid ti
ssues that preceded rejection in all experiments by a range of 7-14 da
ys. The use of DBMC from transgenic mice allowed a unique opportunity
to monitor the kinetics of DBMC-derived chimerism. The presence of chi
merism in the skin of mice in temporal association with chronic allogr
aft rejection suggests that chimerism per se is not a reliable index o
f allogeneic unresponsiveness.