The role of CD45RO in antithymocyte globulin's stimulation of primitive haemopoietic cells.
We have found that antithymocyte globulin (ATG), an equine antibody with proven efficacy in aplastic anaemia (AA), has a direct stimulatory effect on primitive haemopoietic cells from normal donors. This growth stimulation may be mediated via anti-CD45RO activity present in the ATG preparation. Addition of unabsorbed ATG enhanced colony growth at 21 d in the blast colony forming cell (Bl-CFC) assay. Prior absorption of ATG by incubation with the CD45RO+ MOLT-4 cell line resulted in the loss of enhancement. Absorption by MOLT-4 cells preincubated with anti-CD45RO mAb, UCHL-1, restored ATG's stimulatory effect. The Bl-CFC could also be stimulated to grow by the addition of UCHL-1 directly. Incubation of the primitive haemopoietic cells for 4 h with ATG was associated with a decline in the antigenic density of CD45RO, a tyrosine phosphatase. This down-regulation may upset the balance between growth factor-induced tyrosine kinase activation and tyrosine phosphate dephosphorylation resulting in increased growth of primitive cells, a possible factor in the sustained recovery of haemopoiesis seen in AA patients after ATG treatment.
Huang
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Department of Medicine, Duke University Medical Center, Durham, N.C. 27710.
Mold
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D000741:Anemia, Aplastic / Q000097:blood / Q000276:immunology / Q000473:pathology; D000961:Antilymphocyte Serum / Q000276:immunology / Q000627:therapeutic use*; D002455:Cell Division; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000502:physiology*
D000961:Antilymphocyte Serum; D017493:Leukocyte Common Antigens