The contact-mediated response of peripheral-blood monocytes to preactivated T cells is suppressed by serum factors in rheumatoid arthritis.
Stimulation of monocytes/macrophages after cell contact with preactivated T cells has been suggested to contribute to the excessive TNF-alpha production in rheumatoid arthritis (RA). In this study, T cell-contact-dependent TNF-alpha production by peripheral-blood monocytes in vitro was investigated and found to be significantly lower in treated and untreated patients with RA than in healthy controls. This suppression was not due to a general deficiency of monocytes to respond, because responses to lipopolysaccharide were comparable in patients and controls. In agreement with the pivotal role of TNF-alpha in RA, T cell-dependent induction of TNF-alpha in synovial macrophages was fivefold to tenfold higher than in peripheral-blood monocytes from either patients or controls. The decreased response of peripheral-blood monocytes from patients with RA was found to be mediated by inhibitory serum factors, because the addition of patient sera to monocytes from healthy controls suppressed TNF-alpha response in the co-culture assay. Preincubation of monocytes from healthy controls with RA serum was sufficient to suppress the subsequent TNF-alpha response in T cell co-cultures, indicating that inhibitory factors do indeed bind to monocyte surfaces, which might represent a regulatory counter-action of the immune system to the long-standing and consuming autoimmune process in RA. There are some indications that apolipoprotein A-1 might be part of this regulatory system.
Rossol
Manuela
M
Department of Medicine IV, University of Leipzig, Leipzig, Germany. mrossol@gmx.net
Kaltenhäuser
Sylke
S
Scholz
Roger
R
Häntzschel
Holm
H
Hauschildt
Sunna
S
Wagner
Ulf
U
D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D007596:Joints; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008875:Middle Aged; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D016632:Apolipoprotein A-I; D014409:Tumor Necrosis Factor-alpha