DEVELOPMENT OF A NEW ANTI-CD4 MONOCLONAL-ANTIBODY (YG23) WHICH INHIBITS THE FORMATION OF COLONIES OF HUMAN BONE-MARROW PROGENITOR CELLS

We have previously reported CD4 expression in CD34+ hematopoietic prog enitor cells and suggested a role of CD4 in normal hematopoiesis and i ts possible relationship with the pathogenesis of acquired immunodefic iency syndrome (AIDS), To investigate whether CD4 expression in bone m arrow progenitor cells can explain bone marrow suppression in AIDS, mo noclonal antibodies (mAbs) against human CD4 were developed by immuniz ing Balb/c mice with human thymocytes, Three mAbs completely blocked t he binding of Leu3a antibody, a well-known anti-CD4 mAb, to thymocytes , which indicates overlap between the epitopes recognized by these and Leu3a antibodies. Interestingly, one of these mAbs, YG23, significant ly inhibited colony formation of human bone marrow progenitor cells tr eated with GM-CSF, This is the first demonstration that ligation of CD 4 by an anti-CD4 mAb suppresses GM-CSF mediated proliferation and diff erentiation of human hematopoietic progenitor cells by modifying the i ntracellular signaling pathway through CD4 molecules, Based on these f indings, we propose that alteration of CD4 signaling by either cross-l inked gp120 or antibodies directed against a certain epitope shared wi th the YG23 binding site of the CD4 molecule may play a role in bone m arrow dysfunction in AIDS patients.