Three patients with severe combined immunodeficiency (SCID) received transplants of HLA haplotype-mismatched parental bone marrow depleted of T lymphocytes by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion. Two patients achieved durable engraftment with reconstitution of both humoral and cell-mediated immunity. Neither of these patients developed graft versus host disease (GVHD). The third patient achieved only a transient engraftment with concomitant development of mitogen-responsive lymphocytes of paternal origin. Our experience indicates that depletion of T lymphocytes by this technique can abrogate the potential of histoincompatible marrow grafts to induce lethal GVHD without limiting immunologic reconstitution. It also provides further evidence of nonimmune mechanisms of graft resistance that may necessitate preparative treatment of patients with SCID before transplantation with HLA- mismatched marrow cells.

Five children with primary deficiencies of T cell function were studied to assess the effects of highly purified exogenous Interleukin 2 (IL 2) on their in vitro T cell responses. The lymphocytes from one child with Nezelof's T cell deficiency demonstrated absence of endogenous IL 2 production and improved proliferative responses to mitogen or alloantigen in the presence of exogenous IL 2. Moreover, during in vitro mixed lymphocyte culture in the presence of exogenous IL 2, his lymphocytes were able to develop into cytotoxic effector cells. A second child with Nezelof's syndrome demonstrated a different type of defect. The lymphocytes from this child had less impairment of endogenous IL 2 production. Although IL 2 increased the proliferation of his cells in response to PHA, similar augmentation was not seen after stimulation with OKT3 or alloantigen. In cell-mediated cytotoxicity assays, after mixed lymphocyte culture, natural killer-like activity was strongly boosted in the cultures that contained IL 2, but T cell-mediated cytotoxicity was not. The lymphocytes from three patients with severe combined immunodeficiency did not show improved proliferative responses in the presence of IL 2. Thus, only one of the five patients demonstrated the combination of defective endogenous IL 2 production, but preservation of the ability to respond appropriately to exogenous IL 2. This child may therefore have suffered from a T cell defect pathophysiologically similar to that seen in nude or aged mice.