期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1982
卷号：79
期号：19
页码：6047-6051
DOI：10.1073/pnas.79.19.6047
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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-versus-host disease (GVHD), which is mediated by alloreactive donor T cells, may occur. In an attempt to prevent GVHD in one SCID patient lacking a matched donor, we treated maternal haplomismatched bone marrow with a unique nonmitogenic T-cell-specific monoclonal antibody (anti-T12) and complement to remove mature T cells. Despite the removal of greater than 99% mature T cells, the child developed significant life-threatening GVHD, which was terminated by a 5-day course of intravenous anti-T12. Subsequently, immune reconstitution occurred by 6 wk: the mature circulating T cells proliferated in response to soluble and allo-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. We conclude that HLA-mismatched transplantation for SCID can be undertaken if mature alloreactive donor T lymphocytes are depleted before and after bone marrow grafting.
