Figure 3.

Model for the Immune Response Mechanism Against AAV Vectors

Cooperation between pDCs (that sense the AAV genome via TLR9 and produce T1 IFN), cDCs (that present antigen), and CD4⁺ T helper cells (that provide co-stimulation via the CD40-CD40L pathway) leads to activation of CD8⁺ T cells. Antibody formation also depends on CD4⁺ T helper cells and is augmented by activation of moDCs, resulting in IL-1β and IL-6 pro-inflammatory cytokine production, and is modulated by T1 IFN. Abbreviations are as follows: IFNAR-1, interferon α/β receptor 1; cDC, conventional dendritic cell; pDC, plasmacytoid dendritic cell; IFN, interferon; TLR, Toll-like receptor; MyD88, myeloid differentiation primary response protein 88; MHC, major histocompatibility complex; moDC, monocyte-derived dendritic cell; and CD, cluster of differentiation.