The systemic and SmD183-119-autoantigen-specific cytokine memory of Th cells in SLE patients.
OBJECTIVE
The aim of the study was to analyse the cytokine memory of T-cells derived from systemic lupus erythematosus (SLE) patients and healthy donors enriched for autoantigen-specific T-cells by in vitro stimulation with SmD1(83-119), a common autoantigen in SLE.


METHODS
Autoreactive CD3+ T-cells derived from 37 SLE patients and 14 healthy donors were enriched by repetitive ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with SmD1(83-119). For control, PBMCs were stimulated only with interleukin-2 (IL-2). After two rounds of antigenic stimulation, cultures were stimulated with PMA/ionomycin to probe the cytokine memory by intracellular cytokine staining. Frequencies of cytokine-expressing T-cells were analysed and, in SLE patients, compared with disease activities and autoantibody levels.


RESULTS
Comparing the cytokine memory in the cultures, SLE patients displayed higher frequencies of tumour necrosis factor-alpha (TNF-alpha)+ T-cells than healthy donors and the frequencies correlated with disease activity. Frequencies of SmD1(83-119)-specific TNF-alpha+ T-cells and of memory T-cells expressing interferon-gamma (IFN-gamma) correlated with serum anti-dsDNA antibody levels. The frequencies of IL-10 expressing SmD1(83-119)-specific T-cells were lower among PBMCs of SLE patients. Relatively higher frequencies of IL-10+ T-cells in SLE patients correlated with low disease activities, and low anti-dsDNA and anti-SmD1(83-119) antibody concentrations in culture supernatants.


CONCLUSIONS
The memory of autoreactive SmD1(83-119)-specific and unspecific stimulated peripheral Th cells for re-expression of cytokines is shifted towards more cells expressing TNF-alpha and less IL-10+ cells, when compared SLE patients with normal donors. This shift towards proinflammatory memory effector Th cells correlates with disease severity and humoral autoimmunity.
Langer
S
S
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Schumannstr. 20/21, D-10117 Berlin, Germany.
Langnickel
D
D
Enghard
P
P
Undeutsch
R
R
Burmester
G R
GR
Hiepe
F
F
Radbruch
A
A
Riemekasten
G
G
D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055517:snRNP Core Proteins
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D017252:CD3 Complex; D016207:Cytokines; D010446:Peptide Fragments; D017411:Ribonucleoproteins, Small Nuclear; C526409:SNRPD1 protein, human; D014409:Tumor Necrosis Factor-alpha; D055517:snRNP Core Proteins; D016753:Interleukin-10