Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response.

Autor: van Bergen CA, van Luxemburg-Heijs SA, de Wreede LC, Eefting M, von dem Borne PA, van Balen P, Heemskerk MH, Mulder A, Claas FH, Navarrete MA, Honders WM, Rutten CE, Veelken H, Jedema I, Halkes CJ, Griffioen M, Falkenburg JH
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2017 Feb 01; Vol. 127 (2), pp. 517-529. Date of Electronic Publication: 2017 Jan 09.
DOI: 10.1172/JCI86175
Abstrakt: Patients with leukemia who receive a T cell-depleted allogeneic stem cell graft followed by postponed donor lymphocyte infusion (DLI) can experience graft-versus-leukemia (GVL) reactivity, with a lower risk of graft-versus-host disease (GVHD). Here, we have investigated the magnitude, diversity, and specificity of alloreactive CD8 T cells in patients who developed GVL reactivity after DLI in the absence or presence of GVHD. We observed a lower magnitude and diversity of CD8 T cells for minor histocompatibility antigens (MiHAs) in patients with selective GVL reactivity without GVHD. Furthermore, we demonstrated that MiHA-specific T cell clones from patients with selective GVL reactivity showed lower reactivity against nonhematopoietic cells, even when pretreated with inflammatory cytokines. Expression analysis of MiHA-encoding genes showed that similar types of antigens were recognized in both patient groups, but in patients who developed GVHD, T cell reactivity was skewed to target broadly expressed MiHAs. As an inflammatory environment can render nonhematopoietic cells susceptible to T cell recognition, prevention of such circumstances favors induction of selective GVL reactivity without development of GVHD.
Competing Interests: The authors have declared that no conflict of interest exists.
Databáze: MEDLINE