Tipping the balance toward transplantation tolerance: in vivo therapy using a mutated IL-2.

Immune tolerance to allogenic transplanted tissues remains elusive, and therapeutics promoting CD4+FOXP3+ Tregs are required to achieve this ultimate goal. In this issue of the JCI, Efe and colleagues engineered an Fc domain fused to a human mutein IL-2 (mIL-2-Fc) bearing mutations that confer preferential binding to the high-affinity IL-2 receptor expressed on Tregs. In vivo mIL-2-Fc therapy effectively heightened mouse, monkey, and human Treg numbers, promoted tolerance to minor antigen mismatched skin grafts in mice, and synergized with immunosuppressive drugs used in the clinic.

Donor-derived regulatory dendritic cell infusion modulates effector CD8 T cell and NK cell responses after liver transplantation.

Immune cell-based therapies are promising strategies to facilitate immunosuppression withdrawal after organ transplantation. Regulatory dendritic cells (DCreg) are innate immune cells that down-regulate alloimmune responses in preclinical models. Here, we performed clinical monitoring and comprehensive assessment of peripheral and allograft tissue immune cell populations in DCreg-infused live-donor liver transplant (LDLT) recipients up to 12 months (M) after transplant.

Tracking kidney transplant fitness.

An implantable bioelectronic device detects the early signs of kidney transplant rejection in rats.

Tissue-resident memory T cell maintenance during antigen persistence requires both cognate antigen and interleukin-15.

Our understanding of tissue-resident memory T (T) cell biology has been largely developed from acute infection models in which antigen is cleared and sterilizing immunity is achieved. Less is known about T cells in the context of chronic antigen persistence and inflammation. We investigated factors that underlie T maintenance in a kidney transplantation model in which T cells drive rejection.

Manufacturing and validation of Good Manufacturing Practice-compliant regulatory dendritic cells for infusion into organ transplant recipients.

Background Aims: Regulatory (or "tolerogenic") dendritic cells (DCregs) are a highly promising, innovative cell therapy for the induction or restoration of antigen-specific tolerance in immune-mediated inflammatory disorders. These conditions include organ allograft rejection, graft-versus-host disease following bone marrow transplantation and various autoimmune disorders. DCregs generated for adoptive transfer have potential to reduce patients' dependence on non-specific immunosuppressive drugs that can induce serious side effects and enhance the risk of infection and certain types of cancer.