Antigen-specific exosomes act via antigen-presenting cells

There is a new study following up immune-suppression by antigen-specific exosomes coated with antibody light chains delivering inhibitory miRNA-150. It shows that the target is antigen-presenting macrophages, to then inhibit the function of antigen specific effector T cells.

This follows prior work by Krzysztof Bryniarski from the Jagellonian College of Medicine in Kracow Poland working in the laboratory of Phil Askenase at Yale.  This work showed that suppressive CD8+ T cells from antigen tolerized mice inhibited effector T cells via release of inhibitory miRNA-150 contained in antibody light chain coated nano-vesicle exosomes.

New studies by this group, now led by Katarzyna Nazimek show that the suppressive exosomes do not act directly on the effector T cells.  Instead, the exosomes act indirectly by targeting and then altering antigen decorated presenting macrophages that then regulate the T cells. Accordingly, the suppressive exosomes were inactive in mice depleted of macrophages. Further, in vitro studies showed inhibition of antigen-induced proliferation of the effector T cells by macrophages that had been pretreated with the suppressive exosomes.  These results demonstrate an essential role of antigen presenting cells in exosome-mediated antigen-specific suppression of effector T cells targeted by the Exosome surface antibody light chains to deliver inhibitory miRNA-150 for subsequent suppression of accompanying antigen-specific effector T cells.

exosome rna

Nazimek K, Ptak W, Nowak B, Ptak M, Askenase PW, Bryniarski K. (2015) Macrophages play an essential role in antigen-specific immune suppression mediated by t cd8+ cell-derived exosomes. Immunology [Epub ahead of print]. [abstract]

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