title: Lymphocyte reconstitution following non-myeloablative hematopoietic stem cell transplantation follows two patterns depending on age and donor/recipient chimerism.
abstract: The effect of mixed chimerism on the pace of post-transplant immune reconstitution is unknown. Using flow cytometry, recall and neo-antigen vaccine responses, and T cell receptor recombination excision circle (TREC) quantification, we evaluated phenotypic and functional characteristics of T and B cells in nine patients following non-myeloablative, HLA-identical peripheral blood stem cell transplantation for chronic granulomatous disease. Engraftment of T cell, B cell, and myeloid lineages proceeded at similar paces within each patient, but engraftment kinetics segregated patients into two groups: adults, who became full donor T cell chimeras before 6 months (rapid engrafters) and children, who became full donor T cell chimeras after 6 months or not at all (slow engrafters). Quantitative B cell recovery was achieved by 6 weeks after transplantation in children, but was delayed until 1 year in adults. Early quantitative B cell recovery was not accompanied by an early humoral immune response to tetanus toxoid (TT). Emergence of TT-specific T cell responses coincided with naive T cell reconstitution, as measured by CD4/CD45RA T cell recovery and TREC quantification. These data suggest that immune reconstitution occurs faster in pediatric patients who have prolonged mixed hematopoietic chimerism compared to adults, who have rapid donor stem cell engraftment.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Building 10 Room 11N113, Bethesda, MD 20892-1886, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Savage
authors.forename: J J
authors.initials: JJ
authors.lastname: Bleesing
authors.forename: D
authors.initials: D
authors.lastname: Douek
authors.forename: M R
authors.initials: MR
authors.lastname: Brown
authors.forename: G M
authors.initials: GM
authors.lastname: Linton
authors.forename: H L
authors.initials: HL
authors.lastname: Malech
authors.forename: M E
authors.initials: ME
authors.lastname: Horwitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006105:Granulomatous Disease, Chronic / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D007136:Immunoglobulins; D019653:Myeloablative Agonists