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 IgE molecules can be generated in vitro by stimulating resting naive CD8 T+ cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE responses in vivo. In addition, adoptive transfer of the IgE specific CTLs to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTLs provide a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocytes (CTLs) in vitro. The CTLs induced by peptides identified from CD40L can kill activated CD4+ T cells. In vitro generated CTLs specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo. In contrast, CTLs induced by antigenic peptides derived from IgE specifically inhibit IgE responses, and adoptive transfer of CD40L-specific CTL to NOD mice at early age delay the development of diabetes in NOD mice. In vitro generated CTLs specific for non-tumor self-antigens expressed on activated CD4+ T cells regulate immune responses in vivo.