Reconstitution after transplantation with T-lymphocyte-depleted HLA haplotype-mismatched bone marrow for severe combined immunodeficiency.

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Abstract
Severe combined immunodeficiency (SCID) is potentially correctable by bone marrow transplantation if a patient has a suitable histocompatible donor. In the absence of an HLA-matched donor, lethal graft-vs.-host disease (GVHD), which is mediated by alloreactive donor T cells, may occur. To prevent GVHD in 1 SCID patient lacking a matched donor, maternal haplomismatched bone marrow was treated with a unique nonmitogenic T-cell-specific monoclonal antibody (anti-T12) and complement to remove mature T cells. Despite the removal of > 99% mature T cells, the child developed significant life-threatening GVHD, which was terminated by a 5-day course of i.v. anti-T12. Subsequently, immune reconstitution occurred by 6 wk; the mature circulating T cells proliferated in response to soluble anti-antigens in vitro and provided help for B-cell immunoglobulin synthesis. The patient was removed from a protective environment and discharged without evidence of further infection. Both HLA and chromosomal analyses showed that the circulating cells in the patient were of maternal origin. More importantly, the maternal T cells were no longer reactive with recipient cells. Mixing experiments indicated that the state of tolerance that resulted in this chimera was not due to active suppression. HLA-mismatched transplantation for SCID can be undertaken if mature alloreactive donor T lymphocytes are depleted before and after bone marrow grafting.