564. T Cell Immunity Using Transgenic B Lymphocytes

Abstract

Top of pageAbstract T cell responses begin when precursor T cells recognize antigen on specialized antigen-presenting cells (APCs) and differentiate into effector cells. Here we present evidence that primary naive B lymphocytes can be genetically-programmed using non-viral DNA and turned into powerful APCs with a dual capacity of synthesis and presentation of antigen to T cells in vivo. We found that a single intravenous injection of transgenic B lymphocytes in naive immunocompetent mice activates T cell responses reproducibly and specifically even at very low cell doses (102). Interestingly, these T cell responses can occur in the absence of dendritic cells and result in immunological memory with protective effector functions. Using plasmid DNA coding for the dominant epitope (NP366-374) of the influenza virus nucleoprotein, we were able to study the characteristics of the CD8 T cell memory response in C57Bl/6 mice and its relation to protection. We found that memory CTL responses are protective at very low dose (3102 cells/inoculum), and that protection in particular is mediated by CD8 T cells of the central memory type. These findings disclose new directions in the use of plasmid DNA for interventions aimed at producing immunological effects in vivo. Key aspects of the new working principles are the direct involvement of antigen presenting cells (transgenic B lymphocytes) in an in vivo process characterized by (1) a capacity of the injected lymphocytes to home to secondary lymphoid organs, (2) a protracted self-renewing capacity of antigen synthesis processing and presentation directly at the site of immune induction (the secondary lymphoid organs), and (3) the potential for mobilizing a generalized immune response. These characteristics together with the fact that the generation of immunity by transgenic B lymphocytes occurs within the spatio-temporal geometry of organized secondary lymphoid organs, enable this new approach with a spectrum of potential applications for vaccination against viruses and cancer in humans.