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Inducer3
*
Section of Rheumatology, Department of Medical Sciences, Uppsala University; and
Section of Immunology, Department of Veterinary Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden
Patients with active systemic lupus erythematosus (SLE) have signs
of an ongoing IFN-
production, that may be of pathogenic
significance in the disease. We previously showed that SLE patients
have an IFN--inducing factor in blood, probably consisting of
complexes containing anti-DNA Abs and immunostimulatory DNA. The
DNA component could be derived from apoptotic cells, because SLE
patients have been reported to have both increased apoptosis and
reduced clearance of apoptotic cell material. In the present study, we
therefore investigated whether apoptotic cells, together with IgG from
SLE patients, could act as an IFN- inducer in normal PBMC in vitro.
We found that apoptotic cells of the myeloid leukemia cell line U937 as
well as four other cell lines (MonoMac6, H9, Jurkat, U266) could induce
IFN- production in PBMC when combined with IgG from SLE patients.
The IFN- production by PBMC was much enhanced when PBMC were
costimulated by IFN-2b. The ability of IgG from different SLE
patients to promote IFN- induction by apoptotic U937 cells was
associated with the presence of anti-ribonucleoprotein Abs, but not
clearly with occurrence of anti-DNA Abs. These results suggest that
apoptotic cells in the presence of autoantibodies can cause production
of a clearly immunostimulatory cytokine, which is IFN-. This
mechanism for induction of IFN- production could well be operative
also in vivo, explain the IFN- production seen in SLE patients, and
be important in the pathogenesis of SLE.
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