Transplantation of thymus tissue in complete DiGeorge syndrome.
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.
Markert
M L
ML
Department of Pediatrics, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC 27710, USA. marke001@mc.duke.edu
Boeck
A
A
Hale
L P
LP
Kloster
A L
AL
McLaughlin
T M
TM
Batchvarova
M N
MN
Douek
D C
DC
Koup
R A
RA
Kostyu
D D
DD
Ward
F E
FE
Rice
H E
HE
Mahaffey
S M
SM
Schiff
S E
SE
Buckley
R H
RH
Haynes
B F
BF
D000015:Abnormalities, Multiple / Q000276:immunology / Q000601:surgery; D001706:Biopsy; D002455:Cell Division; D004062:DiGeorge Syndrome / Q000276:immunology / Q000601:surgery*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000637:transplantation*
D008934:Mitogens; D011948:Receptors, Antigen, T-Cell