title: Essential role of the thymus to reconstitute naive (CD45RA+) T-helper cells after human allogeneic bone marrow transplantation.
abstract: To contribute to the understanding of the role of the thymus in humans in the reconstitution of naive (CD45RA+) T cells after bone marrow transplantation (BMT), we compared T-cell regeneration in a unique situation, namely a thymectomized cancer patient (15 years old), with that of thymus-bearing patients after allogeneic BMT. These cases shared features of transplantation (total body irradiation, HLA-matched donors, and graft-versus-host disease prophylaxis with cyclosporine A) and all had an uncomplicated post-transplantation course. As shown by fluorescence-activated cell sorting analyses, the thymectomized host failed to reconstitute CD45RA+ T-helper cells even 24 months after BMT (11% CD45RA+ of CD4+ cells). In this patient, preferentially CD45RO+ cells contributed to the recovery of CD4+ cells (206 of 261/microL at 6 months and 463 of 558/microL at 24 months after BMT, CD45RA+ of CD4+ cells), whereas CD45RA+ cells remained low (<60/microL). In contrast, nine thymus-bearing hosts (5 children and 4 adults) examined between 6 and 24 months after BMT effectively reconstituted CD4+/CD45RA+ cells according to their normal age-related range (> or = 28% in adults and > or = 50% in children). Five of these were analyzed sequentially at 6 and 9 months after BMT. Within this period, CD45RA+ cells increasingly contributed to the recovery of CD4+ cells (median, +21%), even when total CD4+ cells decreased. With respect to T-cytotoxic/suppressor cells, the thymectomized host retained the capacity to recover CD45RA+ cells (137 of 333/microL at 6 months and 596 of 1,046/microL at 24 months after BMT, CD45RA+ of CD8+ cells), a proportion similar to that seen in thymus-bearing hosts. These findings suggest that a thymus-independent pathway exists to regenerate CD45RA+ T-cytotoxic/suppressor cells, but residual thymus is essential to reconstitute naive (CD45RA+) T-helper cells after BMT in humans.
authors.affiliation: University Children's Hospital Innsbruck, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Heitger
authors.forename: N
authors.initials: N
authors.lastname: Neu
authors.forename: H
authors.initials: H
authors.lastname: Kern
authors.forename: E R
authors.initials: ER
authors.lastname: Panzer-Grümayer
authors.forename: H
authors.initials: H
authors.lastname: Greinix
authors.forename: D
authors.initials: D
authors.lastname: Nachbaur
authors.forename: D
authors.initials: D
authors.lastname: Niederwieser
authors.forename: F M
authors.initials: FM
authors.lastname: Fink
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000517:prevention & control; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007223:Infant; D017493:Leukocyte Common Antigens; D008297:Male; D012038:Regeneration; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D015703:Antigens, CD; D016572:Cyclosporine; D017493:Leukocyte Common Antigens