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Activated T cells enhance interferon-α production by plasmacytoid dendritic cells stimulated with RNA-containing immune complexes
  1. Dag Leonard1,
  2. Maija-Leena Eloranta1,
  3. Niklas Hagberg1,
  4. Olof Berggren1,
  5. Karolina Tandre1,
  6. Gunnar Alm2,
  7. Lars Rönnblom1
  1. 1Department of Medical Sciences, Science for Life Laboratories, Rheumatology, Uppsala University, Uppsala, Sweden
  2. 2Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden
  1. Correspondence to Dr Dag Leonard, Department of Medical Sciences, Rheumatology, Uppsala University, Rudbecklaboratoriet C11 2fl, Dag Hammarskjölds väg 20, Uppsala S-75185, Sweden; dag.leonard{at}medsci.uu.se

Abstract

Objectives Patients with systemic lupus erythematosus (SLE) have an ongoing interferon-α (IFN-α) production by plasmacytoid dendritic cells (pDCs). We investigated whether T cells can promote IFN-α production by pDCs.

Methods Human pDCs were stimulated with immune complexes (ICs) containing U1 small nuclear ribonucleic proteins particles and SLE-IgG (RNA-IC) in the presence of T cells or T cell supernatants. T cells were activated by anti-CD3/CD28 antibodies or in a mixed leucocyte reaction. IFN-α and other cytokines were determined in culture supernatants or patient sera with immunoassays. The effect of interleukin (IL) 3 and granulocyte-macrophage-colony-stimulating factor (GM-CSF) on pDCs was examined by the use of antibodies, and the expression of CD80/CD86 was determined using flow cytometry.

Results Activated T cells and supernatants from activated T cells increased IFN-α production by >20-fold. The stimulatory effect of T cell supernatants was reduced after depletion of GM-CSF (81%) or by blocking the GM-CSF receptor (55%–81%). Supernatant from activated T cells, furthermore, increased the frequency of CD80 and CD86 expressing pDCs stimulated with RNA-IC from 6% to 35% (p<0.05) and from 10% to 26% (p<0.01), respectively. Activated SLE T cells enhanced IFN-α production to the same extent as T cells from healthy individuals and a subset of patients with SLE had increased serum levels of GM-CSF.

Conclusions Activated T cells enhance IFN-α production by RNA-IC stimulated pDCs via GM-CSF and induce pDC maturation. Given the increased serum levels of GM-CSF in a subset of patients with SLE, these findings suggest that activated T cells may upregulate type I IFN production in SLE.

  • Systemic Lupus Erythematosus
  • T Cells
  • Cytokines

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