Title
In-vivo t-cell activation by anti-cd3 monoclonal-antibody induces soluble tnf receptor release in mice : effects of pentoxifylline, methylprednisolone, anti-tnf, and anti-ifn-gamma antibodies
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Baltimore, Md ,
Subject
Human medicine
Source (journal)
The journal of immunology. - Baltimore, Md
Volume/pages
153(1994) :2 , p. 499-506
ISSN
0022-1767
ISI
A1994NW18300004
Carrier
E
Target language
English (eng)
Abstract
Injection of anti-CD3 is accompanied by an increase in systemic TNF, a mediator of the physiologic changes induced by anti-CD3 injection. Various mechanisms have been reported to be responsible for TNF inactivation and clearance. Recently, it has become evident that circulating soluble TNFRs (P55 and P75), which are known to increase in response to TNF inducers such as LPS, represent a natural protection mechanism against circulating TNF. Here we show that triggering the TCR by anti-CD3 injection results in a strong induction of both systemic TNF and soluble TNFR release. Maximal levels of TNF were reached after 2 h (10 ng/ml). Maximum levels of P55 (450 pg/ml) were reached between 0.5 and 8 h, whereas the highest levels of P75 were reached after 2 h (28 ng/ml). Because TNF and IFN-gamma are supposed to be involved in the pathophysiology of the anti-CD3 response, we investigated the influence of in vivo neutralization of TNF and IFN-gamma. Injection of mAb to TNF and IFN-gamma significantly reduced systemic TNF levels and both soluble TNFR levels. Two inhibitors of anti-CD3 induced TNF release; steroids and pentoxifylline both reduced TNF levels and P75 levels without affecting P55 levels. The results show that T cell activation induces both system ic TNF release and release of both soluble TNFRs. Although TNF and IFN-gamma are involved in this mechanism, their role does not seem to be crucial.
E-info
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