Activated T cells enhance interferon-α production by plasmacytoid dendritic cells stimulated with RNA-containing immune complexes.
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.



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.



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.



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.
Department of Medical Sciences, Science for Life Laboratories, Rheumatology, Uppsala University, Uppsala, Sweden.
Dag
D
Leonard
Department of Medical Sciences, Science for Life Laboratories, Rheumatology, Uppsala University, Uppsala, Sweden.
Maija-Leena
ML
Eloranta
Department of Medical Sciences, Science for Life Laboratories, Rheumatology, Uppsala University, Uppsala, Sweden.
Niklas
N
Hagberg
Department of Medical Sciences, Science for Life Laboratories, Rheumatology, Uppsala University, Uppsala, Sweden.
Olof
O
Berggren
Department of Medical Sciences, Science for Life Laboratories, Rheumatology, Uppsala University, Uppsala, Sweden.
Karolina
K
Tandre
Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Gunnar
G
Alm
Department of Medical Sciences, Science for Life Laboratories, Rheumatology, Uppsala University, Uppsala, Sweden.
Lars
L
Rönnblom
D000936:Antigen-Antibody Complex / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008213:Lymphocyte Activation; D012313:RNA / Q000276:immunology*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000936:Antigen-Antibody Complex; D016898:Interferon-alpha; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
Cytokines; Systemic Lupus Erythematosus; T Cells