A prospective comparison of immune reconstitution in pediatric recipients of positively selected CD34+ peripheral blood stem cells from unrelated donors vs recipients of unmanipulated bone marrow from related donors.
Positively selected CD34(+) hematopoietic stem cells from unrelated donors (UD-HSCT) have been successfully transplanted, but little is known about immune reconstitution in this setting. Here we report a prospective comparison of immune reconstitution in recipients of UD-HSCT and of unmanipulated bone marrow from matched sibling donors (MSD-BMT). T-cell reconstitution occurred more than 100 days later in the UD-HSCT than in the MSD-BMT group. The first T cells after UD-HSCT were almost exclusively CD45RO(+) HLA-DR(+), whereas early-emerging T cells after MSD-BMT more frequently expressed CD62L, CD28, and CD25. In both groups, numbers of CD45RA(+) naive T cells increased after 180 days. After UD-HSCT, the T-cell-receptor (TCR)-repertoire was severely skewed and showed significantly reduced diversity during the first year, but only minor abnormalities were seen after MSD-BMT. TCR-diversity increased simultaneously with the number of naive T cells. In both groups, we observed transient expansions of gammadelta T cells. B cells were reconstituted more rapidly in UD-HSCT than in MSD-BMT recipients, whereas the rapidity of NK-cell reconstitution was similar in the two groups. In summary, T-cell reconstitution was slower after UD-HSCT than after MSD-BMT because of the delayed recovery of early memory-type T cells with reduced TCR-diversity, whereas naive T-, NK-, and B cells were reconstituted similarly in the two groups.
Eyrich
M
M
Pediatric Stem Cell Transplant Program, Children's Hospital, University of Tuebingen, Germany.
Leiler
C
C
Lang
P
P
Schilbach
K
K
Schumm
M
M
Bader
P
P
Greil
J
J
Klingebiel
T
T
Handgretinger
R
R
Niethammer
D
D
Schlegel
P G
PG
D000293:Adolescent; D018952:Antigens, CD34 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000378:metabolism; D001854:Bone Marrow Cells / Q000473:pathology; D018106:CD28 Antigens / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D007156:Immunologic Memory; D007223:Infant; D007694:Killer Cells, Natural / Q000378:metabolism; D019041:L-Selectin / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D010641:Phenotype; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013234:Stem Cells / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014019:Tissue Donors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D018952:Antigens, CD34; D018106:CD28 Antigens; D017252:CD3 Complex; D006684:HLA-DR Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D019041:L-Selectin; D017493:Leukocyte Common Antigens