Low-Dose IL-2 Therapy in Transplantation, Autoimmunity, and Inflammatory Diseases

  • J Immunol. 2019 Dec 1;203(11):2749-2755. doi: 10.4049/jimmunol.1900733.
Maryam Tahvildari  1  2 ,  Reza Dana  3
Affiliations
  • 1. Kresge Eye Institute, Wayne State University, Detroit, MI 48201; and.
  • 2. Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
  • 3. Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114 [email protected].
PMID: 31740549 DOI: 10.4049/jimmunol.1900733
Abstract

Regulatory T cells (Tregs) play a central role in the induction and maintenance of immune homeostasis and self-tolerance. Tregs constantly express the high-affinity receptor to IL-2. IL-2 is a pleiotropic cytokine and a key survival factor for Tregs. It maintains Tregs' suppressive function by promoting Foxp3 expression and subsequent production of immunoregulatory cytokines. Administration of low-dose IL-2 is shown to be a promising approach to prevent allograft rejection and to treat autoimmune and inflammatory conditions in experimental models. The combination of IL-2 with its mAb (JES6-1) has also been shown to increase the t 1/2 of IL-2 and further enhance Treg frequencies and function. Low-dose IL-2 therapy has been used in several clinical trials to treat conditions such as hepatitis C vasculitis, graft-versus-host disease, type 1 diabetes, and systemic lupus erythematosus. In this paper, we summarize our findings on low-dose IL-2 treatment in corneal allografting and review recent studies focusing on the use of low-dose IL-2 in transplantation, autoimmunity, and Other inflammatory conditions. We also discuss potential areas of further investigation with the aim to optimize current low-dose IL-2 regimens.

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