Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency

N Engl J Med. 2000 May 4;342(18):1325-32. doi: 10.1056/NEJM200005043421804.


Background: Immune function can be restored in infants with severe combined immunodeficiency by transplantation of unfractionated bone marrow from HLA-identical donors or T-cell-depleted marrow stem cells from haploidentical donors, with whom there is a single haplotype mismatch, without the need for chemotherapy before transplantation or prophylaxis against graft-versus-host disease. The role of the thymus in this process is unknown.

Methods: We analyzed the phenotypes of circulating T cells and the proliferative responses of peripheral-blood mononuclear cells to phytohemagglutinin in 83 patients with severe combined immunodeficiency who received allogeneic marrow transplants without T-cell ablation from related donors over an 18-year period. We also tested for the presence of episomes of T-cell antigen receptors (extrachromosomal DNA circles formed during intrathymic T-cell development) to assess thymus-dependent T-cell reconstitution.

Results: Before and early after transplantation, the numbers of circulating T cells were low, with a predominance of mature CD45RO+ T cells (primarily resulting from the transplacental transfer of maternal cells); T-cell antigen-receptor episomes were undetectable in peripheral-blood mononuclear cells. In 73 of the infants, thymus-derived T cells expressing CD45RA and T-cell antigen-receptor episomes were detected within three to six weeks after transplantation. The mean (+/-SD) value for thymus-dependent T-cell antigen-receptor episomes peaked (at 7311+/-8652 per microgram of peripheral-blood mononuclear-cell DNA) 1 to 2 years after transplantation and declined to low levels (less than 100 episomes per microgram of DNA) within 14 years, as compared with a gradual decline from birth to the age of about 80 years in normal subjects.

Conclusions: The vestigial thymus in infants with severe combined immunodeficiency is functional and can produce enough T cells after bone marrow transplantation to provide normal immune function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant
  • Leukocyte Common Antigens
  • Lymphocyte Count
  • Phenotype
  • Plasmids / analysis
  • Receptors, Antigen, T-Cell / genetics*
  • Severe Combined Immunodeficiency / immunology
  • Severe Combined Immunodeficiency / therapy*
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology*
  • Thymus Gland / physiology


  • Receptors, Antigen, T-Cell
  • Leukocyte Common Antigens