Mechanism of cellular rejection in transplantation

The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance

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