Increased monocyte-dependent suppression of polyclonal activation of B lymphocytes from cystinotic children

In infantile cystinosis the amino acid cystine preferentially accumulates in phagocytic cells, polymorphonuclear leucocytes (PMN) and monocytes, rather than in lymphocytes. We previously described functional abnormalities in the oxidative metabolism and locomotion of cystinotic PMN and monocytes. The present study shows an abnormal lymphocyte polyclonal activation as evidenced by a decreased immunoglobulin (Ig) production and generation of Ig-containing cells (ICC) in cultures of peripheral blood mononuclear cells (PBMC) from cystinotic children upon stimulation with pokeweed mitogen and Staphylococcus aureus Cowan I. However, monocyte depletion from cystinotic PBMC fully reconstituted Ig production and ICC generation, indicating: (1) the presence of an increased monocyte-dependent suppression on lymphocyte polyclonal activation, and (2) that the intrinsic ability of cystinotic lymphocytes to respond to polyclonal stimulation was preserved. The increased cystinotic monocyte-dependent suppressive effect was not mediated by prostaglandin E2 (PGE2) since its production by cystinotic PBMC upon polyclonal activation was not different from that of controls. In addition, the sensitivity of cystinotic lymphocytes to the immunosuppressive effect of varying concentrations of exogenous PGE2 was similar to that of controls. Finally, indomethacin and 2-mercaptoethanol, two agents able to scavenge hydroxyl (.OH) radicals, restored Ig production by cystinotic PBMC, suggesting a role for reactive oxygen species in the increased cystinotic monocyte-dependent suppression.