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

Donor T cells after stem cell transplantation reconstitute by 2 different p athways: by expansion from grafted, mature T cells and by intrathymic matur ation from progenitor cells. This study characterized thymic-dependent reco nstitution of CD4(+) T cells following different transplant modalities in p atients with severe combined immunodeficiency (SCID). Three groups of patie nts were studied: one group after transplantation from human leukocyte anti gen (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 de termining the expression of CD45 isoforms by developing CD4(+) cells in the peripheral blood and in discriminating expanded (CD45RO(+)) and newly gene rated (CD45RA(+)) T cells. Concomitantly, changes in the size of the thymus were evaluated sequentially by ultrasonography. Reconstitution of CD4(+)CD 45RA(+) cells was delayed in all patients far several months, including pat ients after HLA-identical transplantation, and was always paralleled by nor malization of the size of the thymus. No engraftment of donor progenitor ce lls was observed, as studied in one patient transplanted without conditioni ng. CD4(+)CD45RO(+) cells were detected early after transplantation only in patients given unmanipulated grafts. The study showed that thymic-dependen t 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 requir e engraftment of donor-derived CD34(+) cells In the marrow. (Blood. 2000;96 :4344 4349) (C) 2000 by The American Society of Hematology.