Research article

The contact-mediated response of peripheral-blood monocytes to preactivated T cells is suppressed by serum factors in rheumatoid arthritis

Manuela Rossol¹ , Sylke Kaltenhäuser¹ , Roger Scholz² , Holm Häntzschel¹ , Sunna Hauschildt³ and Ulf Wagner¹

¹  Department of Medicine IV, University of Leipzig, Leipzig, Germany

²  Department of Orthopedics, University of Leipzig, Leipzig, Germany

³  Department of Immunobiology, Institute of Zoology, University of Leipzig, Leipzig, Germany

author email corresponding author email

Arthritis Research & Therapy 2005, 7:R1189-R1199doi:10.1186/ar1804

Published:	17 August 2005

Abstract

Stimulation of monocytes/macrophages after cell contact with preactivated T cells has been suggested to contribute to the excessive TNF-α production in rheumatoid arthritis (RA). In this study, T cell-contact-dependent TNF-α 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-α in RA, T cell-dependent induction of TNF-α 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-α response in the co-culture assay. Preincubation of monocytes from healthy controls with RA serum was sufficient to suppress the subsequent TNF-α 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.