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Early CD30 signaling is critical for adoptively transferred CD4(+)CD25(+) regulatory T cells in prevention of acute graft-versus-host disease BLOOD Zeiser, R., Nguyen, V. H., Hou, J., Beilhack, A., Zambricki, E., Buess, M., Contag, C. H., Negrin, R. S. 2007; 109 (5): 2225-2233

Abstract

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.

View details for DOI 10.1182/blood-2006-07-038455

View details for Web of Science ID 000244641100067

View details for PubMedID 17068147

View details for PubMedCentralID PMC1801065