Donor natural killer (NK1.1+) cells do not play a role in the suppression of GVHD or in the mediation of GVL reactions after DLI

Bryon D. Johnson, Nabil Dagher, Marja C. Stankowski, Carrie A. Hanke, Robert L. Truitt

Research output: Contribution to journalArticle

Abstract

Donor regulatory T cells (CD3+ αβT-cell receptor [TCR]+) derived from the repopulating host thymus have been shown to be primarily responsible for suppression of GVHD following DLI therapy in murine BMT models. However, natural killer (NK) T cells also have regulatory properties, and a role for NK T cells in suppression of GVH reactivity has not been completely excluded. NK cells may also contribute to the graft-versus-leukemia (GVL) effect associated with DLI therapy. In this study, we used a murine BMT model (C57BL/6 into AKR) to study whether depletion of donor NK cells had any impact on the suppression of GVH reactivity after DLI or on the DLI-induced GVL effect against acute T-cell leukemia. Depletion of donor NK cells was accomplished in vivo by giving DLI-treated bone marrow chimeras multiple injections of anti-NK1.1 monoclonal antibody (MoAb). The chimeras treated with anti-NK1.1 MoAb had significantly fewer splenic NK1.1+ cells than nontreated chimeras, and splenocytes from anti-NK1.1-treated mice were deficient in the ability to generate lymphokine-activated lytic activity. Results presented here showed that NK-cell depletion had no effect on the suppression of GVH reactivity after DLI. When DLI-treated chimeras were challenged with an cute T-cell leukemia, NK-cell depletion had no discernible effect on GVL reactivity. These preclinical data suggest that donor NK cells do not have a significant role in the suppression of GVHD after DLI or in the mediation of GVL reactivity induced by DLI.

Original languageEnglish (US)
Pages (from-to)589-595
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume7
Issue number11
DOIs
StatePublished - Jan 1 2001

Keywords

  • Bone marrow transplantation
  • Donor leukocyte infusion
  • Graft-versus-host disease
  • Graft-versus-leukemia effect
  • NK cells

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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