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

Blood. 2009 Aug 13;114(7):1445-53. doi: 10.1182/blood-2009-01-199323. Epub 2009 May 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bone Marrow Transplantation*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Receptors, Antigen, T-Cell
  • Retrospective Studies
  • Severe Combined Immunodeficiency / blood
  • Severe Combined Immunodeficiency / immunology*
  • Severe Combined Immunodeficiency / therapy*
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Time Factors
  • Transplantation Chimera / blood
  • Transplantation Chimera / immunology*
  • Transplantation, Homologous

Substances

  • Receptors, Antigen, T-Cell