2024-Low dose Interleukin 2 Therapy Fine tuning Treg in Solid Organ Transplantation

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.
(Transplantation 2024;108: 1492–1508).