title: In vitro-induced response patterns of antileukemic T cells: characterization by spectratyping and immunophenotyping.
abstract: Myeloid leukemic cells can be induced to differentiate into leukemia-derived dendritic cells (DCleu) regaining the stimulatory capacity of professional DCs while presenting the leukemic antigen repertoire. But so far, the induced antileukemic T-cell responses are variable both in specificity and in efficacy. In an attempt to elucidate the underlying causes of different T-cell response patterns, T-cell receptor (TR) Vβ chain rearrangements were correlated with the T cells corresponding immunophenotypic profile, as well as their proliferative response and cytolytic capacities. In three different settings, donor T cells, either human leukocyte antigen matched or mismatched (haploidentical), or autologous T cells were repeatedly stimulated with myeloid blasts or leukemia-derived DC/DCleus from the corresponding patients diseased from acute myeloid leukemia (AML). Although no significant differences in T-cell proliferation were observed, the T-cell-mediated cytolytic response pattern varied considerably and even caused blast proliferation in two cases. Spectratyping revealed a remarkable restriction (>75% of normal level) of the CD4+ or CD8+-TR repertoire of blast- or DC/DCleu-stimulated T cells. Although in absolute terms, DC/DCleu stimulation induced the highest grade of restriction in the CD8+ T-cell subset, the CD4+ T-cell compartment seemed to be relatively more affected. But most importantly, in vitro stimulation with DC/DCleu resulted into an identical TR restriction pattern (β chain) that could be identified in vivo in a patient sample 3 months after allo-SCT. Thus, in vitro tests combining functional flow cytometry with spectratyping might provide predictive information about T cellular response patterns in vivo.
authors.affiliation: Faculty of Medical, Department of Paediatric Oncology, Haematology and Immunology, University Dusseldorf, 40225, Dusseldorf, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Reuther
authors.forename: Helga
authors.initials: H
authors.lastname: Schmetzer
authors.forename: Friedhelm R
authors.initials: FR
authors.lastname: Schuster
authors.forename: Pina
authors.initials: P
authors.lastname: Krell
authors.forename: Christine
authors.initials: C
authors.lastname: Grabrucker
authors.forename: Anja
authors.initials: A
authors.lastname: Liepert
authors.forename: Tanja
authors.initials: T
authors.lastname: Kroell
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
authors.forename: Raymund
authors.initials: R
authors.lastname: Buhmann
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003584:Cytological Techniques / Q000379:methods; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*
chemical_list: D011948:Receptors, Antigen, T-Cell