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

Abstract

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.

• Authors: D D Patel, M E Gooding, R E Parrott, K M Curtis, B F Haynes, R H Buckley
• Journal: The New England journal of medicine (N Engl J Med) Vol. 342 Issue 18 Pg. 1325-32 (May 04 2000) ISSN: 0028-4793 [Print] United States
• PMID: 10793165 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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