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Blood, 15 September 2006, Vol. 108, No. 6, pp. 2106-2113.
Prepublished online as a Blood First Edition Paper on June 6, 2006; DOI 10.1182/blood-2006-03-007427.
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Submitted March 6, 2006
Accepted April 26, 2006
Host MHC Class II+ antigen-presenting cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions
Ronjon Chakraverty, Hyeon-Seok Eom, Jessica Sachs, Jennifer Buchli, Pete Cotter, Richard Hsu, Guiling Zhao, and Megan Sykes*
Massachusetts General Hospital/Harvard Medical School
Massachusetts General Hospital
* Corresponding author; email: megan.sykes{at}tbrc.mgh.harvard.edu.
Following bone marrow transplantation, delayed donor leukocyte infusions (DLI) can induce graft-versus-leukemia (GVL) effects without graft-versus-host disease (GVHD). These anti-tumor responses are maximized by the presence of host hematopoietic APC at the time of DLI. Using a tumor-protection model, we demonstrate here that GVL activity following administration of DLI to established mixed chimeras is primarily dependent upon reactivity to allogeneic MHC antigens rather than minor histocompatibility or tumor-associated antigens. CD8+ T cell-dependent GVL responses against an MHC Class II-negative tumor following delayed DLI require CD4+ T cell help and are reduced significantly when host APCs lack MHC Class II expression. CD4+ T cells primed by host APCs were required for maximal expansion of graft-versus-host-reactive CD8+ T cells but not their synthesis of IFN-gamma. In contrast, the GVL requirement for CD4+ T cell help was bypassed almost completely when DLI was administered to freshly irradiated recipients, indicating that the host environment is a major factor in influencing the cellular mechanisms of GVL.
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