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Previous Volume 342:1325-1332 May 4, 2000 Number 18 Next

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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.

Source Information

From the Departments of Medicine (D.D.P., M.E.G., B.F.H.), Immunology (D.D.P., B.F.H., R.H.B.), and Pediatrics (R.E.P., K.M.C., R.H.B.) and the Human Vaccine Institute (D.D.P., B.F.H.), Duke University Medical Center, Durham, N.C.

Address reprint requests to Dr. Patel at Box 3258, Duke University Medical Center, Durham, NC 27710, or at patel003{at}mc.duke.edu.

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