959 ABNORMAL LYMPHOCYTE ACTIVATION IN CARTILAGE HAIR HYPOPLASIA

Abstract

Cartilage-Hair Hypoplasia (CHH) is an autosomal recessive form of short-limbed dwarfism which occurs in increased frequency in the Amish. In previous studies of Amish CHH patients we found markedly decreased lymphocyte proliferative responses to phytohem-agglutinin, concanavalin A (Con A), pokeweed mitogen and allogeneic cells. The present study was undertaken to determine if these abnormalities were due to imbalances in lymphocyte subpopulations or defective lymphocyte activation. Studies on 9 CHH patients with specific monoclonal antibodies revealed a decrease in the absolute number of T- and B-lymphocytes but a normal helper to suppressor cell ratio (OKT4+/OKT8+). The number of monocytes assayed by non-specific esterase, latex ingestion and anti-OKM1 were normal; CHH monocytes functioned normally as helper cells and did not demonstrate suppressor activity when cocultured with CHH or normal T-lymphocytes. CHH lymphocyte membranes bound Con A and the mitogenic monoclonal anti-OKT3 normally, however CHH T-lymphocytes showed markedly reduced proliferative responses to Con A, OKT3, phorbol my-ristate acetate and Ca++ ionophore A23187. CHH B-lymphocytes proliferated poorly after stimulation with S. aureus. These data suggest that CHH lymphocytes have a defect in activation at a post-membrane, post-calcium influx step. CHH lymphocytes may be a useful model for the study of defects in cell proliferation which may also exist in other cells of CHH patients (e.g. chondrocytes).