Details

Autor(en) / Beteiligte

• Dahlke, Marc H.
• Lauth, Oliver S.
• Jäger, Mark D.
• Roeseler, Till
• Timrott, Kai
• Jackobs, Stefan
• Neipp, Michael
• Wonigeit, Kurt
• Schlitt, Hans J.

Titel

In vivo depletion of hematopoietic stem cells in the rat by an anti-CD45 (RT7) antibody

Ist Teil von

• Blood, 2002-05, Vol.99 (10), p.3566-3572

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.