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

  • Heiler S Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Lötscher J Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Kreuzaler M Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Rolink J Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Rolink A Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • 2018-04-20
Published in:
  • Frontiers in immunology. - 2018
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
Animals
Antibodies
Antigen-Antibody Complex
CD8-Positive T-Lymphocytes
Cells, Cultured
Disease Models, Animal
Graft vs Host Disease
Humans
Immunotherapy
Interleukin-2
Lupus Erythematosus, Systemic
Lymphocyte Transfusion
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
T-Lymphocytes, Regulatory
Transplantation, Homologous
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/232593
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