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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 (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 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Carbonaro, D. A. Articles by Kohn, D. B. Search for Related Content PubMed PubMed Citation Articles by Carbonaro, D. A. Articles by Kohn, D. B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 1, 2007 Accepted February 21, 2008 Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunological reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion Denise A. Carbonaro, Xiangyang Jin, Daniel Cotoi, Tiejuan Mi, Xiao-Jin Yu, Dianne C. Skelton, Frederick Dorey, Rodney E. Kellems, Michael R. Blackburn, and Donald B. Kohn* Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, CA, United States Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX, United States Department of Pediatrics, University of Southern California, Keck School of Medicine, Los Angeles, CA, United States * Corresponding author; email: dkohn{at}chla.usc.edu. 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 knock-out model of ADA-deficient SCID. Newborn ADA-deficient pups were transplanted by intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, resulting in long-term survival, multi-system correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1-3% of lymphocytes and myeloid cells were of donor origin and there was not a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Pre-conditioning of neonates with 100-400 cGy of total-body irradiation prior to 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 non-myeloablative bone marrow transplant, which has implications for clinical BMT or gene therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. B. Gaspar, A. Aiuti, F. Porta, F. Candotti, M. S. Hershfield, and L. D. Notarangelo How I treat ADA deficiency Blood, October 22, 2009; 114(17): 3524 - 3532. [Abstract] [Full Text] [PDF]

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