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

Reuther S, Schmetzer H, Schuster FR, et al. In vitro-induced response patterns of antileukemic T cells: characterization by spectratyping and immunophenotyping. Clinical and Experimental Medicine. 2013;13(1):29-48.Myeloid leukemic cells can be induced to differentiate into leukemia-derived dendritic cells (DC(leu)) 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/DC(leus) 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/DC(leu)-stimulated T cells. Although in absolute terms, DC/DC(leu) 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/DC(leu) 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