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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5745-5754. Prepublished online as a Blood First Edition Paper on March 20, 2008; DOI 10.1182/blood-2007-08-103663. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-08-103663v1 111/12/5745    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Carbonaro, D. A. Articles by Kohn, D. B. PubMed PubMed Citation Articles by Carbonaro, D. A. Articles by Kohn, D. B. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion Denise A. Carbonaro1,2, Xiangyang Jin1, Daniel Cotoi1, Tiejuan Mi3, Xiao-Jin Yu1, Dianne C. Skelton1, Frederick Dorey2, Rodney E. Kellems3, Michael R. Blackburn3, and Donald B. Kohn1,2 1 Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital, Los Angeles, CA; 2 Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles; and 3 Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School Adenosine deaminase (ADA)–deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose–dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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