Publication
Title
Down-regulation of interleukin-2 and interferon-gamma and maintenance of interleukin-4 and interleukin-10 production after administration of an anti-CD3 monoclonal antibody in mice
Author
Abstract
Background. Activating anti-CD3 monoclonal antibodies (mAbs), such as OKT3, are potent immunosuppressive agents that are widely used in clinical transplantation. We investigated whether the in vivo induction of T cell unresponsiveness contributes to the immunosuppressive properties of the anti-mouse-CD3 mAb 145-2C11. Methods. After a single in vivo administration of 145-2C11 residual T cells were restimulated in vivo and in vitro to assess cytokine production. Mice were also transplanted with allogeneic skin 9 days after 145-2C11 administration to investigate whether the immunosuppressive properties of the antibody persist after the reexpression of the T cell receptor. Results. Pretreatment with anti-CD3 mAbs caused a profound deficit in both interleukin- (IL) 2 and interferon- (IFN) gamma secretion upon restimulation in vivo, whereas IL 4 was only partially inhibited and IL-10 production was significantly increased. Purified T cells obtained from mice injected with anti-CD3 mAb also displayed deficient IL-2 and IFN-gamma production together with persisting IL-4 and IL-10 secretion. 145-2C11 had immunosuppressive properties that persisted after the reexpression of the T cell receptor because mice transplanted with allogeneic skin 9 days after a single anti-CDS mAb injection still had significantly prolonged graft survival (14.1+/-0.6 days vs. 10.7+/-0.4 days in controls, P<0.02). Blocking IL-4 and IL-10 by neutralizing mAbs further prolonged skin graft survival in mice injected with 145-2-C11 (18.3+/-0.7 vs. 14.8+/-0.6 days, P<0.02). Conclusion. The in vivo administration of the 145-2C11 anti-CDS mAb results in the selective inhibition of Th1-type cytokine secretion upon restimulation, which correlates with a state of immunosuppression. The persistent production of Th2-type cytokines does not contribute to the anti-CD3 mAb-mediated prolonged survival of skin allografts in our experimental model.
Language
English
Source (journal)
Transplantation. - Baltimore, Md, 1963, currens
Publication
Baltimore, Md : 1999
ISSN
0041-1337
1534-6080 [online]
Volume/pages
68:5(1999), p. 677-684
ISI
000082939200014
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
[E?say:metaLocaldata.cgzprojectinf]
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 06.01.2015
Last edited 14.09.2017