title: Distinct contributions of CD4(+) and CD8(+) naive and memory T-cell subsets to overall T-cell-receptor repertoire complexity following transplantation of T-cell-depleted CD34-selected hematopoietic progenitor cells from unrelated donors.
abstract: Normalization of restricted T-cell-receptor (TCR) repertoire is critical following T-cell-depleted (TCD) stem cell transplantation. We present a prospective study analyzing respective contributions of naive and memory T-cell subsets within the CD4(+) and CD8(+) compartments to the evolution of overall TCR-repertoire complexity following transplantation of CD34-selected peripheral blood progenitor cells from unrelated donors. During the first year after transplantation, sorted CD4/45RA, CD4/45R0, CD8/45RA, and CD8/45R0 subsets were analyzed at 3-month intervals for TCR-repertoire complexity by CDR3 size spectratyping. Skew in TCR-repertoire was observed only in early memory-type T cells. CD4(+) and CD8(+) subsets differed in clonal distribution of CDR3 sizes, with rapid Gaussian normalization of bands in CD4/45R0(+) T cells. Naive T cells displayed normal repertoire complexity and contributed significantly to skew correction. Our data provide direct evidence for an important role of de novo maturation of naive T cells in normalization of an initially restricted TCR-repertoire following transplantation of CD34-selected, TCD-depleted peripheral blood progenitors from unrelated donors.
authors.affiliation: Pediatric Stem Cell Transplant Program, University of Tuebingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eyrich
authors.forename: Tanja
authors.initials: T
authors.lastname: Croner
authors.forename: Christine
authors.initials: C
authors.lastname: Leiler
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Dietrich
authors.initials: D
authors.lastname: Niethammer
authors.forename: Paul G
authors.initials: PG
authors.lastname: Schlegel
mesh_terms: D018952:Antigens, CD34; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007223:Infant; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D011948:Receptors, Antigen, T-Cell