Journal
BLOOD
Volume 109, Issue 5, Pages 2225-2233Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-07-038455
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Funding
- NCI NIH HHS [R24 CA092862, P50 CA114747, R24CA92862, R01 CA0800065] Funding Source: Medline
- NHLBI NIH HHS [P01 HL075462] Funding Source: Medline
- NIAID NIH HHS [K08 AI060888] Funding Source: Medline
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Murine CD4(+)CD25(+) regulatory T cells (Treg cells) reduce acute graft-versus-host disease (aGvHD). However, surface molecules critical for suppression are unclear. Deficiency of CD30 (CD30(-/-)) leads to impaired thymic negative selection and augmented T-cell autoreactivity. Therefore, we investigated the role of CD30 signaling in Treg-cell function during aGvHD. Treg cells derived from CD30-/- animals were significantly less effective in preventing aGvHD lethality. Early blockade of the CD30/CD153 pathway with a neutralizing anti-CD153 mAb reduced Treg-mediated protection from proinflammatory cytokine accumulation and donor-type T-cell apoptosis. In vivo bioluminescence imaging demonstrated intact homing but reduced expansion of luciferase-expressing Treg cells when CD153 was blocked during the early phase after adoptive transfer. CD30 surface expression on Treg cells increased with alloantigen exposure, and CD153 expression on recipient-type dendritic cells increased in the presence of a proinflammatory environment. These data demonstrate that early CD30 signaling is critical for Treg-mediated aGvHD protection after major MHC-mismatch bone marrow transplantation.
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