Evidence for engraftment of donor-type multipotent CD34+ cells in a patient with selective T-lymphocyte reconstitution after bone marrow transplantation for B-SCID.
Severe combined immunodeficiencies (SCID), a heterogeneous group of disorders of infancy, are fatal without treatment directed at immunologic reconstitution. Allogeneic bone marrow transplantation (BMT), which is such a treatment presents some unique features in SCID, especially when T-lymphocyte-depleted HLA haploidentical allografts are used. Donor-type T lymphopoiesis, less often B lymphopoiesis, develops, whereas myelopoiesis remains the recipient-type. Little is known about the engrafting cells in this peculiar lymphohematopoietic chimerism and the pathophysiology of the frequent failure of B-lymphocyte reconstitution. To address these issues, we purified CD34+ BM cells from a patient with selective T-lymphocyte reconstitution after HLA haploidentical BMT for B-SCID. Phenotypic analysis of CD34+ cells was performed by flow cytometry, and functional studies of donor- and recipient-type CD34+ cells were performed in vitro. Donor-type CD34+ cells, constituting approximately 2% of the CD34+ cells, were detected; both CD34+ HLA-DR- cells and CD34+ cells coexpressing B-(CD10 and CD19) and T-(CD2 and CD7) lymphocyte-associated cell surface molecules. Donor-type CD34+ cells coexpressing myeloid-associated molecules (CD13, CD14, CD15, and CD33) were undetectable. However, donor-type CD34+ myeloid progenitors could be shown in functional assays. Recipient-type CD34+ cells coexpressing B- and T-lymphocyte- as well as myeloid-associated molecules were detected, but recipient-type CD34+ cells could not be driven into T-lymphocyte differentiation in vitro. These findings provide evidence for engraftment of multipotent stem cells in our patient with B-SCID. Furthermore, the failure of B-lymphocyte reconstitution cannot be explained by lack of donor-type B-lymphocyte progenitors. Donor-type B lymphopoiesis and myelopoiesis are prevented by an unidentified mechanism.
Tjønnfjord
G E
GE
Institute of Transplantation Immunology and Medical Department A, The National Hospital, University of Oslo, Norway.
Steen
R
R
Veiby
O P
OP
Friedrich
W
W
Egeland
T
T
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D006680:HLA Antigens