Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance - PubMed (original) (raw)

. 2003 Feb 1;170(3):1304-12.

doi: 10.4049/jimmunol.170.3.1304.

Dejun Zhou, Thomas E Ichim, Gill H Strejan, Xiaoping Xia, Jinming Yang, Xuyan Huang, Bertha Garcia, David White, Patrick Dutartre, Anthony M Jevnikar, Robert Zhong

Affiliations

Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance

Wei-Ping Min et al. J Immunol. 2003.

Abstract

An active role of T regulatory cells (Treg) and tolerogenic dendritic cells (Tol-DC) is believed important for the induction and maintenance of transplantation tolerance. However, interactions between these cells remain unclear. We induced donor-specific tolerance in a fully MHC-mismatched murine model of cardiac transplantation by simultaneously targeting T cell and DC function using anti-CD45RB mAb and LF 15-0195, a novel analog of the antirejection drug 15-deoxyspergualin, respectively. Increases in splenic Treg and Tol-DC were observed in tolerant recipients as assessed by an increase in CD4(+)CD25(+) T cells and DC with immature phenotype. Both these cell types exerted suppressive effects in MLR. Tol-DC purified from tolerant recipients incubated with naive T cells induced the generation/expansion of CD4(+)CD25(+) Treg. Furthermore, incubation of Treg isolated from tolerant recipients with DC progenitors resulted in the generation of DC with Tol-DC phenotype. Treg and Tol-DC generated in vitro were functional based on their suppressive activity in vitro. These results are consistent with the notion that tolerance induction is associated with a self-maintaining regulatory loop in which Tol-DC induce the generation of Treg from naive T cells and Treg programs the generation of Tol-DC from DC progenitors.

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