Retroviral and Lentiviral Vectors for the Induction of Immunological Tolerance

Figure 5

Main strategies for the induction of immunological tolerance by genetic modification of DCs using retroviral/lentiviral vectors. In this scheme, the most utilised strategies for the induction of immunological tolerance using gene modification of DCs are shown. On top, using lentiviral or retroviral vectors, the expression of immunosuppressive cytokines in DCs can induce the differentiation of antigen-specific Tregs, or in some cases, Th2 cells. In the middle, lentivectors can be used to express constitutive activators or immunosuppressive intracellular signalling pathways leading to the differentiation of suppressive T cells. On the bottom, lentiviral vectors can either deliver short hairpin RNAs targeted towards proinflammatory pathways such as NF-κB, proinflammatory receptors such as BAFF, or inhibitors of cytokine signalling such as SOC3. All these strategies also lead to the development of suppressive T cells. Not shown in any of these schemes, all strategies lead to differentiation of tolerogenic DCs which will either prevent the expansion of cytotoxic CD8 T cells, or induce their apoptosis/anergy.