Generation of normal lymphocyte populations following transplantation of adenosine-deaminase-deficient fetal liver cells.
Adenosine-deaminase-deficient mice were generated to investigate the role of adenosine deaminase (ADA) in lymphocyte maturation and to test treatment options for the severe combined immunodeficiency (SCID) associated with the absence of ADA in man. Whereas either genetic absence or postnatal inhibition of ADA affect primarily the haematopoietic system in both humans and mice, ADA-deficient mice die in the perinatal period. Consequently, we haematopoietically reconstituted lethally irradiated wild-type recipient mice with ADA-deficient fetal liver cells. Although the liver cells of gestational day 14 ADA-deficient murine embryos appeared metabolically deranged, their in vivo and in vitro colony-forming capacities were similar to those of wild-type embryos. Lethally irradiated wild-type mice transplanted with ADA-deficient fetal liver cells appeared immunologically normal. Following mitogen stimulation, their splenocytes and thymocytes were more sensitive to deoxyadenosine than those from wild-type fetal liver chimaeras. This feature, characteristic of ADA-deficiency, indicated that mature and active lymphocytes were generated from ADA-deficient fetal liver cells following transplantation into wild-type hosts. Because approximately 20% of the haematopoietic cells appeared recipient-derived, it can not be concluded that the murine haematopoietic system can do without ADA-producing cells.
Migchielsen
A A
AA
Department of Medical Biochemistry, University of Leiden, The Netherlands,
Knaän-Schanzer
S
S
Breuer
M L
ML
Hershfield
M S
MS
Valerio
D
D
D000243:Adenosine Deaminase / Q000172:deficiency*; D000818:Animals; D017690:Cell Transplantation; D005260:Female; D016332:Fetal Tissue Transplantation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells; D006801:Humans; D008099:Liver / Q000166:cytology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011247:Pregnancy
D000243:Adenosine Deaminase