Prophylactic and Therapeutic Effects of Interleukin-2 (IL-2)/Anti-IL-2 Complexes in Systemic Lupus Erythematosus-Like Chronic Graft-Versus-Host Disease

Front Immunol. 2018 Apr 4:9:656. doi: 10.3389/fimmu.2018.00656. eCollection 2018.

Abstract

Murine chronic graft-versus-host-disease (cGvHD) induced by injection of parental lymphocytes into F1 hybrids results in a disease similar to systemic lupus erythematosus. Here, we have used DBA/2 T cell injection into (C57BL/6 × DBA/2)F1 (BDF1) mice as a model system to test the prophylactic and therapeutic effects of interleukin-2 (IL-2)/anti-IL-2 immune complexes on the course of cGvHD. Our findings demonstrate that pretreatment with Treg inducing JES6/IL-2 complexes render BDF1 mice largely resistant to induction of cGvHD, whereas pretreatment with CD8+ T cell/NK cell inducing S4B6/IL-2 complexes results in a more severe cGvHD. In contrast, treatment with JES6/IL-2 complexes 4 weeks after induction had no beneficial effect on disease symptoms. However, similar treatment with S4B6/IL-2 complexes led to a significant amelioration of the disease. This therapeutic effect seems to be mediated by donor CD8+ T cells. The fact that a much stronger cGvHD is induced in BDF1 mice depleted of donor CD8+ T cells strongly supports this conclusion. The contrasting effects of the two different IL-2 complexes are likely due to different mechanisms.

Keywords: autoantibodies; chronic graft-versus-host-disease; donor CD8+ T cells; host regulatory T cells; immune complex-mediated glomerulonephritis; interleukin-2 receptor; interleukin-2/anti-interleukin-2 complexes; lupus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / metabolism
  • Antigen-Antibody Complex / therapeutic use*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Disease Models, Animal
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / therapy*
  • Humans
  • Immunotherapy / methods*
  • Interleukin-2 / metabolism*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / therapy*
  • Lymphocyte Transfusion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • T-Lymphocytes, Regulatory / immunology*
  • Transplantation, Homologous

Substances

  • Antibodies
  • Antigen-Antibody Complex
  • Interleukin-2