title: Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response.
abstract: 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.
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: van Bergen
authors.forename: Simone A P
authors.initials: SA
authors.lastname: van Luxemburg-Heijs
authors.forename: Liesbeth C
authors.initials: LC
authors.lastname: de Wreede
authors.forename: Matthijs
authors.initials: M
authors.lastname: Eefting
authors.forename: Peter A
authors.initials: PA
authors.lastname: von dem Borne
authors.forename: Peter
authors.initials: P
authors.lastname: van Balen
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
authors.forename: Arend
authors.initials: A
authors.lastname: Mulder
authors.forename: Fransiscus H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Navarrete
authors.forename: Wilhelmina M
authors.initials: WM
authors.lastname: Honders
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Rutten
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.forename: Inge
authors.initials: I
authors.lastname: Jedema
authors.forename: Constantijn J M
authors.initials: CJ
authors.lastname: Halkes
authors.forename: Marieke
authors.initials: M
authors.lastname: Griffioen
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D015778:Minor Histocompatibility Antigens