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Previous Volume 341:1180-1189 October 14, 1999 Number 16 Next

	Full Text PDF Editorial by Weissman, I. L. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background The DiGeorge syndrome is a congenital disorder that affects the heart, parathyroid glands, and thymus. In complete DiGeorge syndrome, patients have severely reduced T-cell function.

Methods We treated five infants (age, one to four months) with complete DiGeorge syndrome by transplantation of cultured postnatal thymus tissue. Follow-up evaluations included immune phenotyping and proliferative studies of peripheral-blood mononuclear cells plus biopsy of the thymus allograft. Thymic production of new T cells was assessed in peripheral blood by tests for T-cell–receptor recombination excision circles, which are formed from excised DNA during the rearrangement of T-cell–receptor genes.

Results After the transplantation of thymus tissue, T-cell proliferative responses to mitogens developed in four of the five patients. Two of the patients survived with restoration of immune function; three patients died from infection or abnormalities unrelated to transplantation. Biopsies of grafted thymus in the surviving patients showed normal morphologic features and active T-cell production. In three patients, donor T cells could be detected about four weeks after transplantation, although there was no evidence of graft-versus-host disease on biopsy or at autopsy. In one patient, the T-cell development within the graft was demonstrated to accompany the appearance of recently developed T cells in the periphery and coincided with the onset of normal T-cell function. In one patient, there was evidence of thymus function and CD45RA+CD62L+ T cells more than five years after transplantation.

Conclusions In some infants with profound immunodeficiency and complete DiGeorge syndrome, the transplantation of thymus tissue can restore normal immune function. Early thymus transplantation — before the development of infectious complications — may promote successful immune reconstitution.

Source Information

From the Department of Pediatrics, Division of Allergy and Immunology (M.L.M., A.L.K., T.M.M., M.N.B.), the Department of Pathology (L.P.H.), the Department of Immunology (M.L.M., D.D.K., F.E.W.), the Department of Surgery (H.E.R., S.M.M.), and the Duke Comprehensive Cancer Center (M.L.M., L.P.H., D.D.K., F.E.W.), Duke University Medical Center, Durham, N.C.; the Department of Pediatrics, University of Vienna, Vienna, Austria (A.B.); and the Department of Medicine, University of Texas Southwestern Medical Center, Dallas (D.C.D., R.A.K.). Other authors were Sherrie E. Schiff, B.S., Miami Children's Hospital, Miami; Rebecca H. Buckley, M.D., Department of Pediatrics, Division of Allergy and Immunology, Department of Immunology, and the Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, N.C.; and Barton F. Haynes, M.D., Department of Immunology and Department of Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, and the Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, N.C.

Address reprint requests to Dr. Markert at Box 3068, Duke University Medical Center, Durham, NC 27710, or at marke001{at}mc.duke.edu.

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