title: Identification of non-naïve CD4+CD45RA+ T cell subsets in adult allogeneic haematopoietic cell transplant recipients.
abstract: The study of thymic-dependent pathways of T cell reconstitution in T cell replete haematopoietic cell transplant (HCT) recipients in previous studies was complicated by the transfer of naïve CD4(+)CD45RA(+) T cells with the stem cell graft. However, direct quantification of thymic output has been enabled by measurement of T cell receptor excision circles (TREC). We analysed T cell reconstitution using T cell phenotyping and TREC quantification in 12 T cell-replete HCT recipients 6-53 years of age during the first 12 months post transplant. We have identified a novel subpopulation of CD4(+)CD45RA(+) T cells in the peripheral blood of these HCT recipients with expansions of this subset being more pronounced in older recipients. The recovery of classical naïve CD4(+)CD45RA(+) T cells was dependent on thymic output whereas this novel CD4(+)CD45RA(+) subpopulation arose independently of thymic output and displayed effector function and phenotype. These results suggest that CD4(+)CD45RA(+) effector populations exist, similar to the CD8(+)CD45RA(+) effector subset, and that the CD45RA antigen should not be used alone to define naïve CD4(+) T cells when monitoring T cell reconstitution in T cell replete HCT recipients. Furthermore, these results raise important questions regarding the role of the thymus in regulating T cell homeostasis in older HCT recipients and normal individuals.
authors.affiliation: 1Anthony Nolan Research Institute, London, UK.
authors.forename: P R
authors.initials: PR
authors.lastname: Fallen
authors.forename: R F
authors.initials: RF
authors.lastname: Duarte
authors.forename: L
authors.initials: L
authors.lastname: McGreavey
authors.forename: M
authors.initials: M
authors.lastname: Potter
authors.forename: M
authors.initials: M
authors.lastname: Ethell
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
authors.forename: J A
authors.initials: JA
authors.lastname: Madrigal
authors.forename: P J
authors.initials: PJ
authors.lastname: Travers
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015704:CD4 Antigens / Q000032:analysis; D002648:Child; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000502:physiology; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D008212:Lymphocyte Depletion; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D012038:Regeneration; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology*; D014184:Transplantation, Homologous
chemical_list: D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens