PMID- 11110711 OWN - NLM STAT- MEDLINE DCOM- 20010118 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 96 IP - 13 DP - 2000 Dec 15 TI - Similar pattern of thymic-dependent T-cell reconstitution in infants with severe combined immunodeficiency after human leukocyte antigen (HLA)-identical and HLA-nonidentical stem cell transplantation. PG - 4344-9 AB - Donor T cells after stem cell transplantation reconstitute by 2 different pathways: by expansion from grafted, mature T cells and by intrathymic maturation from progenitor cells. This study characterized thymic-dependent reconstitution of CD4(+) T cells following different transplant modalities in patients with severe combined immunodeficiency (SCID). Three groups of patients were studied: one group after transplantation from human leukocyte antigen (HLA)-identical siblings with unmanipulated grafts without conditioning, a second group after transplantation from HLA-nonidentical parents with T-cell-depleted grafts without preconditioning, and a third group with prior conditioning. Reconstitution of the T-cell compartment was monitored by determining the expression of CD45 isoforms by developing CD4(+) cells in the peripheral blood and in discriminating expanded (CD45RO(+)) and newly generated (CD45RA(+)) T cells. Concomitantly, changes in the size of the thymus were evaluated sequentially by ultrasonography. Reconstitution of CD4(+)CD45RA(+) cells was delayed in all patients for several months, including patients after HLA-identical transplantation, and was always paralleled by normalization of the size of the thymus. No engraftment of donor progenitor cells was observed, as studied in one patient transplanted without conditioning. CD4(+)CD45RO(+) cells were detected early after transplantation only in patients given unmanipulated grafts. The study showed that thymic-dependent T-cell maturation in these patients with SCID runs an autonomous course, independent of graft manipulation, of major HLA disparities, and of whether conditioning is used or not. In addition, thymic maturation may not require engraftment of donor-derived CD34(+) cells in the marrow. (Blood. 2000;96:4344-4349) FAU - Muller, S M AU - Muller SM AD - Department of Pediatrics, University Hospital of Ulm, Ulm, Germany. FAU - Kohn, T AU - Kohn T FAU - Schulz, A S AU - Schulz AS FAU - Debatin, K M AU - Debatin KM FAU - Friedrich, W AU - Friedrich W LA - eng PT - Journal Article PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (HLA Antigens) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - EC 3.1.3.48 (Leukocyte Common Antigens) SB - IM MH - Adolescent MH - Adult MH - CD4-Positive T-Lymphocytes/cytology MH - Child MH - Child, Preschool MH - Chimera MH - Female MH - Graft Survival MH - Granulocyte Colony-Stimulating Factor/pharmacology MH - HLA Antigens/*genetics MH - *Hematopoiesis MH - *Hematopoietic Stem Cell Transplantation MH - Histocompatibility MH - Humans MH - Infant MH - Leukocyte Common Antigens/analysis MH - Male MH - Severe Combined Immunodeficiency/*therapy MH - T-Lymphocyte Subsets/*cytology MH - Thymus Gland/*cytology/diagnostic imaging MH - Time Factors MH - Transplantation Conditioning MH - Ultrasonography EDAT- 2000/12/09 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/12/09 11:00 PHST- 2000/12/09 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/12/09 11:00 [entrez] AID - S0006-4971(20)48192-3 [pii] PST - ppublish SO - Blood. 2000 Dec 15;96(13):4344-9.