Cordyceps militaris modulates presentation of exogenous antigen associated with MHC class I and MHC class II pathway in dendritic cells. (78.28)

Abstract

Cordyceps militaris has been used in traditional medicine to treat numerous diseases and reported to have antitumor and immunomodulatory activities in vivo and in vitro. The precise mechanism of its immune response activities is unclear. The water extract of Cordyceps militaris (CME) and cordycepin (3'-deoxyadenosine) were prepared. Cordycepin, nucleoside analogue, is a metabolite of C. militaris, whereas CME is included the cordycepin 1.3 ng/mg. How CME or cordycepin modulated immune reaction mechanism in antigen presenting cells (APCs) by ability to present exogenous antigens in association with the major histocompatibility complexes (MHC) in vitro and ex-vivo were examined. Microencapsulated ovalbumin (OVA) was efficiently captured, processed and presented on both MHC class I as well as MHC class II molecules. DC 2.4 cells (H-2Kb) or bone marrow- drived DCs (BM-DCs) generated from the BM cells of C57BL/6 mouse (H-2Kb) were cultured in the presence of CME or codycepin with OVA-microspheres, and the amount of OVA peptide - MHC class I complexes was measured by T cell hybridoma, CD8 OVA 1.3 T cell, that recognizes the OVA-H-2Kb complex and IL-2 production. The increment of the phagocytotic activity and the expression of MHC molecules on DCs by CME (12.5 ~ 200 μg/ml) were shown, while suppression of its activity had shown by cordycepin. CME also increased IL-2 production when we examined the effects of CME on CD4+ T cells. On the other hand, cordycepin inhibited CD4+ T cell responses in a concentration of between 5μg to 40μg. The present study demonstrates the modulation of cross priming capability could be a target of therapeutic immunoregulation. Key words: Cordyceps militaris, cross presentation, immunomodulator