Blood Journal
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Immunization with host-type CD8α+ dendritic cells reduces experimental acute GVHD in an IL-10–dependent manner

  1. Tomomi Toubai1,
  2. Chelsea Malter1,
  3. Isao Tawara1,
  4. Chen Liu2,
  5. Evelyn Nieves1,
  6. Kathleen P. Lowler1,
  7. Yaping Sun1, and
  8. Pavan Reddy1
  1. 1Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor; and
  2. 2Department of Pathology, University of Florida College of Medicine, Gainesville

Abstract

Little is known about the role of active immunization in suppressing undesirable immune responses. Because CD8α+ dendritic cells (DCs) suppress certain immune responses, we tested the hypothesis that immunization of donors with host-derived CD8α+ DCs will reduce host-specific donor T-cell responses. BALB/c T cells from the animals that were immunized with B6 CD8α+ DCs demonstrated, in vitro and in vivo, significantly reduced proliferation and secretion of inflammatory cytokines but showed enhanced secretion of interleukin-10 (IL-10). The responses against third-party and model antigens were preserved demonstrating antigen specificity. The in vivo relevance was further demonstrated by the reduction on graft-versus-host disease (GVHD) in both a major histocompatibility complex–mismatched clinically relevant BALB/c → B6 model and major histocompatibility complex–matched, minor-mismatched C3H.SW → B6 model of GVHD. Immunization of the donors that were deficient in IL-10 (IL-10−/−) or with CD8α+ DCs from B6 class II (class II−/−) failed to reduce T-cell responses, demonstrating (1) a critical role for secretion of IL-10 by donor T cells and (2) a direct contact between the T cells and the CD8α+ DCs. Together, these data may represent a novel strategy for reducing GVHD and suggest a broad counterintuitive role for vaccination strategies in mitigating undesirable immune responses in an antigen-specific manner.

  • Submitted June 24, 2009.
  • Accepted October 26, 2009.
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