In vitro-induced response patterns of antileukemic T cells: characterization by spectratyping and immunophenotyping

Clin Exp Med. 2013 Feb;13(1):29-48. doi: 10.1007/s10238-012-0180-y. Epub 2012 Mar 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Cytological Techniques / methods
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology
  • Flow Cytometry
  • Humans
  • Immunophenotyping*
  • Leukemia, Myeloid, Acute / immunology*
  • Receptors, Antigen, T-Cell / analysis*

Substances

  • Receptors, Antigen, T-Cell