Effect of In Vivo Expansion of Regulatory T Cells with IL-2/anti-IL-2 Antibody Complex Plus Rapamycin on Experimental Autoimmune Uveoretinitis

Ocul Immunol Inflamm. 2021 Nov 17;29(7-8):1520-1529. doi: 10.1080/09273948.2020.1757119. Epub 2020 May 27.

Abstract

Purpose: To determine the effect of injection of IL-2/anti-IL-2 antibody (IL-2 complex) together with rapamycin on the development of experimental autoimmune uveoretinitis (EAU).Methods: C57BL/6J mice were immunized with human interphotoreceptor retinoid-binding protein peptide. The immunized mice were injected intraperitoneally with PBS, IL-2 complex, rapamycin, or IL-2 complex/rapamycin on days 1, 2, 3, and 4 (induction phase) or days 10, 11, 12, and 13 (effector phase) after immunization.Results: Expansion of CD4+Foxp3+ regulatory T cells in draining lymph nodes was observed in IL-2 complex and IL-2 complex/rapamycin-treated mice. Although injection of IL-2 complex alone was not capable of decreasing the clinical score of EAU, injection of IL-2 complex/rapamycin significantly delayed the onset of EAU. In contrast, the treatment with IL-2 complex alone or IL-2 complex/rapamycin during effector phase failed to suppress EAU.Conclusions: These findings suggest the potential limitations of IL-2 complex or IL-2 complex/rapamycin during EAU.

Keywords: Experimental autoimmune uveoretinitis; Foxp3; IL-2; rapamycin; regulatory T cells.

MeSH terms

  • Animals
  • Antibodies / therapeutic use
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Disease Models, Animal
  • Drug Combinations
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology
  • Immunosuppressive Agents / therapeutic use
  • Injections, Intraperitoneal
  • Interleukin-2 / immunology*
  • Interleukin-2 / therapeutic use*
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Retinitis / drug therapy*
  • Retinitis / immunology
  • Sirolimus / therapeutic use*
  • T-Lymphocytes, Regulatory / immunology*
  • Uveitis / drug therapy*
  • Uveitis / immunology

Substances

  • Antibodies
  • Drug Combinations
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunosuppressive Agents
  • Interleukin-2
  • Sirolimus