CD28/B7 Interactions Are Required for Sustaining the Graft-Versus-Leukemia Effect of Delayed Post-Bone Marrow Transplantation Splenocyte Infusion in Murine Recipients of Myeloid or Lymphoid Leukemia Cells

Bruce R. Blazar, Patricia A. Taylor, Michael W. Boyer, Angela Panoskaltsis-Mortari, James P. Allison, Daniel A. Vallera

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59 Scopus citations

Abstract

Graft-vs-leukemia (GVL) can reduce relapse rates after bone marrow transplantation (BMT). Delayed lymphocyte infusion (DLI) post-BMT can mediate a potent GVL effect with less graft-vs-host disease (CVHD) than would be observed if given early post-BMT. In vivo CD28/B7 blockade can reduce GVHD lethality, and B7 ligand expression can augment an antitumor immune response in mice. To examine the role of CD28/B7 interactions in DLI-mediated GVL, we established murine allogeneic BMT models in C57BL/6 (B6) recipients of C1498 (B6 acute myeloid leukemia) or EL4 (B6 acute T cell leukemia) that closely mimic human GVL. Recipients of C1498 and DLI had a marked reduction in relapse. CVL was blocked by anti-B7 mAb infusion. In contrast recipients of EL4 cells and B10.BR DLI had a more modest GVL effect. The forced expression of B7-1 on EL4 cells markedly augmented the GVL effect of DLI, in contrast to the forced expression of B7-2 on EL4 cells. Relapse rates observed in recipients of C1498-B7-1 and DLI were significantly lower than in recipients of parental C1498 cells. We conclude that the administration of anti-B7 mAbs may impair the GVL effect of DLI and that the forced expression of B7-1 ligands stimulates a GVL effect without adversely affecting the GVHD lethality effect of DLI.

Original languageEnglish (US)
Pages (from-to)3460-3473
Number of pages14
JournalJournal of Immunology
Volume159
Issue number7
StatePublished - Oct 1 1997

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