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 Blood, 13 August 2009, Vol. 114, No. 7, pp. 1445-1453.
Prepublished online as a Blood First Edition Paper on May 11, 2009; DOI 10.1182/blood-2009-01-199323.

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TRANSPLANTATION

Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras

Marcella Sarzotti-Kelsoe1, Chan M. Win2, Roberta E. Parrott3, Myriah Cooney3, Barry K. Moser4, Joseph L. Roberts3, Gregory D. Sempowski5, and Rebecca H. Buckley1,3

Departments of 1 Immunology, 2 Surgery, and 3 Pediatrics, 4 Cancer and Leukemia Group B Statistical Center, and 5 Department of Medicine, Duke University Medical Center, Durham, NC

Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B, and sometimes NK-cell function. Nonablative human leukocyte antigen–identical or rigorously T cell–depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T-cell development in the recipients, leading to long-term survival. We reported previously that normal T-cell numbers, function, and repertoire developed by 3 to 4 months after transplantation in SCID patients, and the repertoire remained highly diverse for the first 10 years after BMT. The T-cell receptor diversity positively correlated with T-cell receptor excision circle levels, a reflection of thymic output. However, the fate of thymic function in SCID patients beyond 10 to 12 years after BMT remained to be determined. In this greater than 25-year follow-up study of 128 patients with 11 different molecular types of SCID after nonconditioned BMT, we provide evidence that T-cell function, thymic output, and T-cell clonal diversity are maintained long-term.


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Related Article in Blood Online:

TRECing long-term success in SCID
Frances T. Hakim
Blood 2009 114: 1287-1288. [Full Text] [PDF]



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