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

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, minormismatched 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. © 2010 by The American Society of Hematology.