Abstract:
: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.
journal_name
Bloodjournal_title
Bloodauthors
Toubai T,Malter C,Tawara I,Liu C,Nieves E,Lowler KP,Sun Y,Reddy Pdoi
10.1182/blood-2009-06-229708subject
Has Abstractpub_date
2010-01-21 00:00:00pages
724-35issue
3eissn
0006-4971issn
1528-0020pii
blood-2009-06-229708journal_volume
115pub_type
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