Publications [#177520] of Bruce A Sullenger

Papers Published

1. J Lee, CM Dollins, D Boczkowski, BA Sullenger, S Nair, Activated B cells modified by electroporation of multiple mRNAs encoding immune stimulatory molecules are comparable to mature dendritic cells in inducing in vitro antigen-specific T-cell responses., Immunology, vol. 125 no. 2 (October, 2008), pp. 229-40, ISSN 1365-2567 [doi]
   (last updated on 2010/07/15)

   Abstract:
   Ex-vivo-activated B cells are an alternative source of antigen-presenting cells (APCs) and a potential replacement for dendritic cells (DCs) in immunotherapy. However, the ability of ex-vivo-activated B cells to function as potent APCs has been a concern, especially when compared to DCs. Our study investigated whether modification of activated B cells with immune stimulatory molecules could enhance the ability of activated B cells to stimulate T cells. We show that murine splenic B cells, activated with a combination of Toll-like receptor agonist and agonistic anti-CD40, stimulated antigen-specific CD8+ T cells more efficiently than cells activated with Toll-like receptor agonist or anti-CD40 alone, probably by down-regulation of the immune regulatory cytokine interleukin-10 (IL-10). However, the activated B cells were still poor T-cell stimulators compared to mature DCs. Therefore, we modified the activated B cells by simultaneous electroporation of multiple messenger RNAs encoding costimulatory molecules (OX40L and 4-1BBL), cytokines (IL-12p35 and IL-12p40) and antigen. We found that de novo expression or overexpression of OX40L, 4-1BBL and IL-12p70 on activated B cells synergistically enhanced proliferation as well as IL-2 and interferon-gamma production by CD8+ T cells. Furthermore, the RNA-modified activated B cells induced antigen-specific cytotoxic T lymphocyte responses as efficiently as mature DCs in vitro. Unexpectedly, modified activated B cells were inferior to mature DCs at in vivo induction of CD8+ T-cell responses. In summary, activated B cells modified to express immune stimulatory molecules are a potent alternative to DCs in immunotherapy.

   Keywords:
   4-1BB Ligand • Animals • Antigens, CD40 • B-Lymphocytes • CD8-Positive T-Lymphocytes • Cells, Cultured • Cytokines • Cytotoxicity, Immunologic • Dendritic Cells • Electroporation • Immunophenotyping • Lymphocyte Activation • Lymphocyte Cooperation • Membrane Glycoproteins • Mice • Mice, Inbred C57BL • Mice, Transgenic • RNA, Messenger • Spleen • Toll-Like Receptors • Tumor Necrosis Factors • agonists • biosynthesis • genetics • immunology • immunology*