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.

Duke Scholars

Author Andrew T. Huang Medicine, Hematologic Malignancies and Cellular Therapy