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Blood, 15 May 2002, Vol. 99, No. 10, pp. 3566-3572
HEMATOPOIESIS
In vivo depletion of hematopoietic stem cells in the rat by an
anti-CD45 (RT7) antibody
Marc H. Dahlke,
Oliver S. Lauth,
Mark D. Jäger,
Till Roeseler,
Kai Timrott,
Stefan Jackobs,
Michael Neipp,
Kurt Wonigeit, and
Hans J. Schlitt
From the Klinik für Viszeral- und
Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover,
Germany.
Anti-CD45 monoclonal antibodies (mAbs) are potentially
powerful tools for the depletion of mature leukocytes. As their
application for immunotherapy also depends on their effects on
bone marrow (BM) progeny, the in vivo effects of an anti-CD45 mAb
(anti-RT7a mAb) on BM precursor cells were analyzed in a
rat model. Anti-RT7a mAb treatment was performed in LEW.1W
(RT1u RT7a) rats with the use of different
dosages. In addition, major histocompatibility complex
(MHC)-congenic BM transplantation making use of a diallelic polymorphism (RT7a/RT7b) of rat CD45 was
applied. Following injection of anti-RT7a mAb into normal
LEW.1W rats, T cells were profoundly depleted in blood, lymph nodes,
and spleen, whereas B cells were coated only by the antibody. Single
injection of anti-RT7a mAb in a high dose induced a lethal
aplastic syndrome with severe thrombocytopenia. Rescue of
antibody-treated animals with BM from congenic LEW.1W-7B rats
(RT1u RT7b) and transplantation of BM from
LEW.1W rats pretreated with anti-RT7a mAb into sublethally
irradiated LEW.1W-7B recipients revealed a profound effect of
the mAb on progeny of myeloid and T-cell lineage. Following repeated
antibody treatment of stable mixed chimeras
(RT7b/RT7a), very few RT7a-positive
B cells were still detectable after 6 months and their number declined
during the subsequent year. These observations show that this
anti-RT7a mAb effectively depletes mature T cells as well
as BM precursor cells of myeloid, T-cell, and thrombocytic lineage
after in vivo application. In contrast, mature B cells are not
depleted, but precursors also appear to be eliminated. Overall, the
findings suggest that the anti-RT7a mAb efficiently
depletes early rat hematopoietic stem cells.
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