Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha- producing cells.
Systemic lupus erythematosus (SLE) patients often have continuous production of interferon-alpha (IFN-alpha), but production of in vitro IFN-alpha by peripheral blood mononuclear cells (PBMC) may be varyingly reduced. We here report that IFN-alpha production induced by Herpes simplex virus (HSV) in PBMC resembling immature dendritic cells and designated natural IFN-alpha producing cells (NIPC), was much more affected than that induced by sendai virus (SV) in monocytes. At the cell level, the frequency of HSV-activated NIPC was reduced 70-fold, but residual NIPC produced normal amounts of IFN-alpha (1-2 U/cell). The NIPC frequency increased 10-fold in SLE-PBMC, but not in control PBMC, when co-stimulated by the combination IFN-alpha-gamma and GM- CSF. No spontaneous IFN-alpha production by PBMCs was detected in SLE patients. While no SLE serum factor inhibiting IFN-alpha production was seen, sera of four out of 11 SLE patients induced IFN-alpha production in healthy control PBMC. We propose that the number of NIPC in SLE are reduced in blood because of recruitment to tissues and activation by an endogenous IFN-alpha inducer, as well as because of lack of co-stimulatory cytokines. IFN-alpha produced in SLE could be of pathogenic significance, because autoimmune diseases develop in patients with infections or tumours during IFN-alpha therapy.
Cederblad
B
B
Division of Immunology, Swedish University of Agricultural Sciences.
Blomberg
S
S
Vallin
H
H
Perers
A
A
Alm
G V
GV
Rönnblom
L
L
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000209:etiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D018108:Respirovirus / Q000276:immunology; D018139:Simplexvirus / Q000276:immunology
D001323:Autoantibodies; D016898:Interferon-alpha