TCR triggering modulates the responsiveness and homeostatic proliferation of CD4+ thymic emigrants to IL-7 therapy.

Interleukin-7 (IL-7) is currently used in clinical trials to augment T-cell counts. Paradoxically, elevated systemic IL-7 found in lymphopenic humans is typically insufficient for CD4(+) T-cell regeneration, and thymopoiesis becomes critical in this process. Here we show that the proliferative effect of IL-7 is more pronounced on CD4(+)CD8(-) thymocytes compared with peripheral CD4(+) T cells.

Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation.

The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relation of B220+ NK cells with regard to other NK-cell subsets.

Adoptive transfer of CD4+CD25+ regulatory cells combined with low-dose sirolimus and anti-thymocyte globulin delays acute rejection of renal allografts in Cynomolgus monkeys.

Although donor alloantigen specific Treg cells play an important role in transplant tolerance, therapeutic applications are limited by their low frequency. In this study, isolated Tregs from Cynomolgus monkeys were efficiently expanded by a co-culture system, and maintained suppressive function on the proliferation of CD4(+) effector cells in vitro. Adoptive transfer of expanded donor alloantigen specific Tregs without any immunosuppressants could prolong survival of MHC-mismatched allografts in Cynomolgus monkeys.

Combined therapy of CD4(+)CD25(+) regulatory T cells with low-dose sirolimus, but not calcineurin inhibitors, preserves suppressive function of regulatory T cells and prolongs allograft survival in mice.

Our previous study proved that sirolimus is a potent immunosuppressant which induces long-term allograft survival depends on persistence of alloantigens. CD4(+)CD25(+) regulatory T (Treg) cells are potent suppressors in transplantation. Our objectives focus on whether combined-therapy of Tregs with immunosuppressants could prolong allograft survival in mice.

A novel negative regulatory element in the human collagenase-3 proximal promoter region.

We have identified in the human collagenase-3 promoter a novel negative regulatory element, GAAAAGAAAAAG, designated AGRE (AG-Rich Element). The AGRE site functionality was characterized in human osteoarthritic (OA) chondrocytes as well as four cell lines. The cells were transfected with a plasmid consisting of the first 133 bp of the collagenase-3 promoter and its AGRE mutated or deleted derivatives.