It has been postulated that the resident ''passenger'' leukocytes of h
ematolymphoid origin that migrate from whole organ grafts and subseque
ntly establish systemic chimerism are essential for graft acceptance a
nd the induction of donor-specific nonreactivity. This phenomenon was
augmented by infusing 3x10(8) unmodified donor bone-marrow cells into
40 patients at the time of organ transplantation. Fifteen of the first
18 analyzable patients had sequential immunological evaluation over p
ostoperative intervals of 5 to 17 months, (which included 7 kidney (tw
o with islets), 7 liver (one with islets), and one heart recipient). T
he evolution of changes was compared with that in 16 kidney and liver
nonmarrow controls followed for 4 to 5 months. The generic immune reac
tivity of peripheral blood mononuclear cells (PBMC) was determined by
their proliferative responses to mitogens (PHA, ConA). Alloreactivity
was measured by the recipient mixed lymphocyte reaction (MLR) to donor
and HLA-mismatched third-party panel cells, Based on all 3 tests, the
recipients were classified as donor-specific hyporeactive, intermedia
te, and responsive; patients who were globally suppressed made up a fo
urth category. Eight (53%) of the 15 marrow-treated recipients exhibit
ed progressive modulation of donor-specific reactivity (3 hyporeactive
and 5 intermediate) while 7 remained antidonor-responsive. In the non
marrow controls, 2 (12.5%) of the 16 patients showed donor-specific hy
poreactivity, 10 (62.5%) were reactive, and 4 (25%) studied during a C
MV infection had global suppression of responsiveness to all stimuli.