In VivoImaging of Local Inflammation: Monitoring LPS-Induced CD80/CD86 Upregulation by PET

Purpose The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigen-presenting cells (APC). We investigated whether local APC activation, induced by subcutaneous (s.c.) inoculation of lipopolysaccharides (LPS), can be imaged by positron emission tomography (PET) with CD80/CD86-targeting(64)Cu-labelled abatacept. Procedures Mice were inoculated s.c. with extracellular-matrix gel containing either LPS or vehicle (PBS). Immune cell populations were analysed by flow cytometry and marker expression by RT-qPCR.Cu-64-NODAGA-abatacept distribution was analysed using PET/CT andex vivobiodistribution. Results The number of CD80(+)and CD86(+)immune cells at the LPS inoculation site significantly increased a few days after inoculation. CD68 and CD86 expression were higher at the LPS than the PBS inoculation site, and CD80 was only increased at the LPS inoculation site. CTLA-4 was highest 10 days after LPS inoculation, when CD80/CD86 decreased again. A few days after inoculation,Cu-64-NODAGA-abatacept distribution to the inoculation site was significantly higher for LPS than PBS (4.2-fold). Co-administration of unlabelled abatacept or human immunoglobulin reduced tracer uptake. The latter reduced the number of CD86(+)immune cells at the LPS inoculation site. Conclusions CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs.Cu-64-NODAGA-abatacept PET allowed following APC activation over time.

Automated summary

The study revealed that CD80 and CD86 are upregulated in LPS-induced local inflammation, indicating invasion of activated APCs. Cu-64-NODAGA-abatacept PET technology allows for tracking APC activation over time.