title: Long-term immune reconstitution of naive and memory t cell pools after haploidentical hematopoietic stem cell transplantation.
abstract: Haploidentical hematopoietic stem cell transplantation (HSCT) constitutes an important alternative for patients lacking a human leukocyte antigen (HLA)-matched donor. Although the use of haploidentical donors is increasingly common, the long-term impact of generating a donor-derived immune system in the context of an HLA-mismatched thymic environment remains poorly characterized. We performed an in-depth assessment of immune reconstitution in a group of haploidentical HSCT recipients 4 to 6 years posttransplantation, in parallel with the respective parental donors and age-matched healthy control subjects. Our data show that the proportion of naive and memory subsets in the recipients, both within CD8(+) and CD4(+) T cells, more closely resembled that observed in age-matched control subjects than in the donors. HSCT recipients displayed relatively high signal-joint T cell-receptor excision circle levels and a high frequency of the recent thymic emigrant-enriched CD31(+) subset within naive CD4(+) and naive regulatory T cells. Moreover, CD8(+), CD4(+), and regulatory T cells from HSCT recipients displayed a diverse T cell repertoire. These results support a key role for thymic output in T cell reconstitution. Nevertheless, HSCT recipients had significantly shorter telomeres within a naive-enriched CD4(+) T cell population than age-matched control subjects, despite the similar telomere length observed within the most differentiated CD8(+) and CD4(+) T cell subsets. Overall, our data suggest that long-term immune reconstitution was successfully achieved after haploidentical HSCT, a process that appears to have largely relied on de novo T cell production.
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors: Rita I
authors: RI
authors: Azevedo
authors: Maria V D
authors: MV
authors: Soares
authors: Adriana S
authors: AS
authors: Albuquerque
authors: Rita
authors: R
authors: Tendeiro
authors: Rui S
authors: RS
authors: Soares
authors: Miguel
authors: M
authors: Martins
authors: Dário
authors: D
authors: Ligeiro
authors: Rui M M
authors: RM
authors: Victorino
authors: João F
authors: JF
authors: Lacerda
authors: Ana E
authors: AE
authors: Sousa
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology / Q000601:surgery; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007156:Immunologic Memory; D007938:Leukemia / Q000276:immunology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014019:Tissue Donors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D006680:HLA Antigens