Mechanistic investigations of granzyme A adjuvant effects on γ 9δ 2T cells

Abstract γδ T cells are ideal effector against cancer and pathogens for numerous reasons: they found in blood, mucosa, lymphoid organs, develop memory responses independent of MHC restriction, present antigen, produce cytokines, cytolytic. An obstacle the development biomedical interventions targeting is need an adjuvant that promotes their expansion suitable human use. The routinely used, IL-2, has multiple drawbacks limiting its use vaccination. Our lab shown γ 9δ 2T cells, induced by BCG vaccination, expanded vitro M. tuberculosis, M.bovis(BCG), our lab’s vaccine candidate 6-O-methylglucoselipopolysaccharide (mGLP), presence IL-2. Additionally, inhibit intracellular mycobacterial growth. This inhibition dependent on granzyme A (GzmA) production GzmA alone can We recently identified also promote without exogenous response to mGLP HMBPP, a phosphoantigen stimulates all cells. To identify cell adjuvants, assays were performed using peripheral blood mononuclear dendritic adjuvant. absolute numbers calculated flow cytometry after 7 days culture. ability upon TLR4, CD14, homodimerization, but enzymatic activity. new information broad implications design, promoting responses, understanding role infectious disease cancer. Supported grants from NIH (R01 AI048391) Bill & Melinda Gates Foundation (OP1118659)