The effects of anti-CD43 antibody treatment on in vitro lymphoid and myeloid maturation

Murine CD43 (leukosialin) is a highly glycosylated surface protein expressed on a wide range of hematopoietic cells. Isoforms of CD43, defined by the rat anti-mouse antibodies S7 and S11, appear to be products of post-translational modification and are differentially expressed on murine lymphocytes. Further studies have revealed both S7 and SI 1 to be present on early T cells (triple negative thymocytes), early B cells (pro-B cells), early myeloid cells, and even stem cells (WGA+, B220-, Ly6C- bone marrow cells). Given the wide expression of CD43 molecules on hematopoietic precursors, experiments were performed to assess the effects of anti-CD43 treatment on lymphoid and myeloid development. Sll profoundly inhibited the growth of B lymphocytes in Whitlock-Witte and "switch" cultures, whereas S7 had no effect. Sll, but not S7, also blocked the growth of myeloid cells in both fresh and established Dexter cultures. In contrast, Sll had no effect on either CPU IL-7, or CFU-c assays, indicating that CD43 blockade is operative at an earlier and/or contact-dependent stage. Finally, addition of either S7 or S11 to fetal thymic organ cultures interfered with the maturation of CD4-, CD8- thymocytes to the CD4+, CD8+ stage, and resulted in a modest reduction of cell recovery after 12 days. Together, these results suggest that certain forms of CD43 play a key role in the early stages of lymphocyte and myeloid maturation. Present studies are assessing whether engagement of CD43 on immature cells results in apoptosis.