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Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 3212-3221
Induction of Donor-Type Chimerism and Transplantation Tolerance Across
Major Histocompatibility Barriers in Sublethally Irradiated Mice by
Sca-1+Lin Bone Marrow Progenitor
Cells: Synergism With Non-Alloreactive (Host × Donor)F1 T Cells
Esther Bachar-Lustig,
Hong Wei Li,
Hilit Gur,
Rita Krauthgamer,
Hadar Marcus, and
Yair Reisner
From the Department of Immunology, Weizmann Institute of Science,
Rehovot, Israel.
Induction of transplantation tolerance by means of bone marrow (BM)
transplantation could become a reality if it was possible to achieve
engraftment of hematopoietic stem cells under nonlethal preparatory
cytoreduction of the recipient. To that end, BM facilitating cells,
veto cells, or other tolerance-inducing cells, have been extensively
studied. In the present study, we show that BM cells within the
Sca-1+Lin cell fraction, previously shown
to be enriched for early hematopoietic progenitors, are capable of
reducing specifically antidonor CTL-p frequency in vitro and in vivo,
and of inducing split chimerism in sublethally 7-Gy-irradiated
recipient mice across major histocompatibility complex barriers. The
immune tolerance induced by the Sca-1+Lin
cells was also associated with specific tolerance toward donor-type skin grafts. The minimal number of cells required to overcome the host
immunity remaining after 7 Gy total body irradiation is very large and,
therefore, it may be very difficult to harvest sufficient cells for
patients. This challenge was further addressed in our study by
demonstrating that non-alloreactive (host × donor)F1 T
cells, previously shown to enhance T-cell-depleted BM allografts in
lethally irradiated mice, synergize with
Sca-1+Lin cells in their capacity to
overcome the major transplantation barrier presented by the sublethal
mouse model.
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