EX-VIVO PRIMING FOR GENERATING CYTOTOXIC T LYMPHOCYTES SPECIFIC FOR NON-TUMOR ANTIGENS TO TREAT AUTOIMMUNE AND ALLERGIC DISEASE

摘要

Cytotoxic T lymphocytes (CTLs specific for antigenic peptides derived from IgEmolecule can be generated in vitro by stimulating resting naïve CD8 T celleswith IgE peptides presented by artificial antigen presenting cells. The IgEspecific CTLs lyse the target cells loaded with IgE peptides in vitro andinhibit antigen specific IgE response in vivo. In addition, adoptive transferof the IgE specific CTL to an asthmatic mouse model can inhibit thedevelopment of lung inflammation and airway hypersensitivity. IgE specific CTLprovides a treatment for allergic asthma and other IgE-mediated allergicdiseases. Antigenic peptides identified from non-tumor self-antigens inducespecific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptidesidentified from CD40L can kill activated CD4 T cells. In vitro generated CTLspecific for CD40L inhibit CD4-dependent antibody responses of all isotypes invivo. In contrast, CTL induced by antigenic peptides derived from IgEspecifically inhibit IgE responses, and adoptive transfer of CD40L-specificCTL to NOD mice at early age delay the adoptive transfer of CD40L-specific CTLto NOD mice at early age delay the development of diabetes in NOD mice. Invitro generated CTl specific for non-tumor sel-antigens expressed on activatedCD4 T cells regulate immune responses in vivo.