Systemic administration of a TLR7 ligand leads to transient immune incompetence due to peripheral-blood leukocyte depletion - PubMed (original) (raw)

. 2005 Oct 1;106(7):2424-32.

doi: 10.1182/blood-2005-01-0342. Epub 2005 Jun 23.

Helge Riemann, Yasmin Basoglu, Anja Hillmer, Carsten Weishaupt, Sandra Balkow, Bernd Benninghoff, Beat Ernst, Meike Steinert, Thomas Scholzen, Cord Sunderkötter, Stephan Grabbe

Affiliations

• PMID: 15976181
• DOI: 10.1182/blood-2005-01-0342

Free article

Systemic administration of a TLR7 ligand leads to transient immune incompetence due to peripheral-blood leukocyte depletion

Matthias Gunzer et al. Blood. 2005.

Free article

Abstract

Toll-like receptor (TLR) ligands lead to the induction of proinflammatory cytokines and are potent enhancers of specific immune responses. We show here that a single systemic dose of R-848, a ligand for TLR7, potently enhanced hapten sensitization during the induction of contact hypersensitivity (CHS). However, R-848 administration also resulted in a rapid and almost complete depletion of leukocytes from the blood. This effect was transient and was associated with general induction of endothelial adhesiveness. In response to R-848, endothelial cells up-regulated adhesion molecules in vitro and in vivo and leukocytes exhibited increased rolling on endothelia in R-848-treated animals. Adhesion molecule induction appeared to be a direct effect, because endothelial cells expressed TLR7 in vitro and in vivo. After R-848 treatment, the tissue residence time of leukocytes was markedly prolonged in all major peripheral organs. The resulting transiently reduced availability of peripheral-blood leukocytes (PBLs) (TRAP) significantly inhibited otherwise potent CHS responses until the effector cells returned. Thus, although TLR7 ligands are effective adjuvants for the induction of cell-mediated immunity, they can transiently inhibit the elicitation of localized immune responses, possibly due to a systemic endothelial activation throughout the vasculature.

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