ABSTRACT
Since its initial description as a neurogenic locus in Drosophila, the Notch pathway has been shown to play a central role in cell fate decisions across species, including vertebrates, guiding the differentiation of multiple cell types. In the immune system, its function was first demonstrated during lymphopoiesis, but in recent years this pathway has been shown to still be active in peripheral T-cells. Therapeutic opportunities that could arise from the manipulation of Notch signaling in immune disorders such as autoimmunity, allergy and in cancer immunotherapy and transplantation are discussed.
Subject(s)
Immunotherapy , Membrane Proteins/physiology , T-Lymphocytes/physiology , Animals , DNA , Humans , Hypersensitivity/drug therapy , Hypersensitivity/immunology , Ligands , Membrane Proteins/genetics , Membrane Proteins/immunology , Membrane Proteins/therapeutic use , Receptors, Notch , T-Lymphocytes/immunology , Vaccines/immunology , Vaccines/therapeutic useABSTRACT
We have previously demonstrated that vaccination of mice with plasmid DNA vectors expressing immunodominant mycobacterial genes induced cellular immune responses and significant protection against challenge with Mycobacterium tuberculosis. We demonstrate here, using in vitro-synthesized RNA, that vaccination with DNA or RNA constructs expressing the M. tuberculosis MPT83 antigen are capable of inducing specific humoral and T-cell immune responses and confer modest but significant protection against M. tuberculosis challenge in mice. This is the first report of protective immunity conferred against intracellular bacteria by an RNA vaccine. This novel approach avoids some of the drawbacks of DNA vaccines and illustrates the potential for developing new antimycobacterial immunization strategies.
