title: Evolution of the donor T-cell repertoire in recipients in the second decade after allogeneic stem cell transplantation.
abstract: After allogeneic stem cell transplantation (SCT), T lymphocyte function is reestablished from the donor's postthymic T cells and through thymic T-cell neogenesis. The immune repertoire and its relation to that of the donor have not been characterized in detail in long-term adult SCT survivors. We studied 21 healthy patients in their second decade after a myeloablative SCT for hematologic malignancy (median follow-up, 12 years). Immune profiles were compared with donor samples cryopreserved at transplant and beyond 10 years from SCT. Only one recipient was on continuing immunosuppression. Compared with the donor at transplant, there was no significant difference in CD4, CD8, natural killer, and B-cell blood counts. However, compared with donors, recipients had significantly fewer naive T cells, lower T-cell receptor excision circle levels, fewer CD4 central memory cells, more effector CD8(+) cells, and more regulatory T cells. TCR repertoire analysis showed no significant difference in complexity of TCRVβ spectratype between recipients and donors, although spectratype profiles had diverged with both gain and loss of donor repertoire peaks in the recipient. In conclusion, long-term allogeneic SCT survivors have subtle defects in their immune profile consistent with defective thymic function but compatible with normal health. This study is registered at http://www.clinicaltrials.gov as NCT00106925.
authors.affiliation: Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Robert Quan
authors.initials: RQ
authors.lastname: Le
authors.forename: J Joseph
authors.initials: JJ
authors.lastname: Melenhorst
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.forename: Brenna
authors.initials: B
authors.lastname: Hill
authors.forename: Sarfraz
authors.initials: S
authors.lastname: Memon
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.forename: Aarthi
authors.initials: A
authors.lastname: Shenoy
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Hensel
authors.forename: Eleftheria K
authors.initials: EK
authors.lastname: Koklanaris
authors.forename: Keyvan
authors.initials: K
authors.lastname: Keyvanfar
authors.forename: Frances T
authors.initials: FT
authors.lastname: Hakim
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000293:Adolescent; D000328:Adult; D002469:Cell Separation; D002648:Child; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D014181:Transplantation Immunology / Q000276:immunology*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007136:Immunoglobulins