Immunization with host-type CD8{alpha}+ dendritic cells reduces experimental acute GVHD in an IL-10-dependent manner.
Little is known about the role of active immunization in suppressing undesirable immune responses. Because CD8alpha(+) dendritic cells (DCs) suppress certain immune responses, we tested the hypothesis that immunization of donors with host-derived CD8alpha(+) DCs will reduce host-specific donor T-cell responses. BALB/c T cells from the animals that were immunized with B6 CD8alpha(+) 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 CD8alpha(+) 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 CD8alpha(+) 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.
Toubai
Tomomi
T
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
Malter
Chelsea
C
Tawara
Isao
I
Liu
Chen
C
Nieves
Evelyn
E
Lowler
Kathleen P
KP
Sun
Yaping
Y
Reddy
Pavan
P
D000208:Acute Disease; D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007111:Immunity, Cellular / Q000235:genetics; D007116:Immunization, Passive / Q000379:methods; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D016753:Interleukin-10