Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras.
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.
Departments of Immunology, Duke University Medical Center, Durham, NC 27710, USA. msarzott@duke.edu
Marcella
M
Sarzotti-Kelsoe
Chan M
CM
Win
Roberta E
RE
Parrott
Myriah
M
Cooney
Barry K
BK
Moser
Joseph L
JL
Roberts
Gregory D
GD
Sempowski
Rebecca H
RH
Buckley
D016026:Bone Marrow Transplantation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D011948:Receptors, Antigen, T-Cell; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D018183:Transplantation Chimera / Q000097:blood / Q000276:immunology*; D014184:Transplantation, Homologous
D011948:Receptors, Antigen, T-Cell