Low-Dose Interleukin-2 Therapy: Fine-tuning Treg in Solid Organ Transplantation?

Author:

Amini Leila12,Kaeda Jaspal1,Weber Olaf3,Reinke Petra12

Affiliation:

1. Berlin Center for Advanced Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.

2. Berlin Institute of Health – Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.

3. Institute of Molecular Medicine and Experimental Immunology (IMMEI), University of Bonn, Bonn, Germany.

Abstract

Regulatory T cells (Treg), a subset of CD4+ T cells, are potent regulators of immune reactions, which have been shown to be a promising therapeutic alternative to toxic immunosuppressive drugs. Data support the utility of Treg in managing immunopathologies, including solid organ transplant rejection, graft-versus-host disease, and autoimmune disorders. Notably, reports suggest that interleukin-2 (IL-2) is critical to survival of Treg, which constitutively express high levels of CD25, that is, the IL-2 receptor α-chain, and are exquisitely sensitive to IL-2, even at very low concentrations in contrast to effector T cells, which only upregulate IL-2 receptor α-chain on activation. This has led to the notion of using low doses of exogenous IL-2 therapeutically to modulate the immune system, specifically Treg numbers and function. Here, we summarize developments of clinical experience with low-dose IL-2 (LD-IL-2) as a therapeutic agent. So far, no clinical data are available to support the therapeutic use of LD-IL-2 therapy in the solid organ transplant setting. For the latter, fine-tuning by biotechnological approaches may be needed because of the narrow therapeutic window and off-target effects of LD-IL-2 therapy and so to realize the therapeutic potential of this molecule.

Funder

EU

Publisher

Ovid Technologies (Wolters Kluwer Health)

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