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The Korean Association of Immunobiologists (대한면역학회)
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Enhancing T Cell Immune Responses by B Cell-based Therapeutic Vaccine Against Chronic Virus Infection

  • Kim, Min Ki (System Immunology Laboratory, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Lee, Ara (System Immunology Laboratory, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Hwang, Yu Kyeong (Cell Therapy Team, Mogam Biotechnology Institute) ;
  • Kang, Chang-Yuil (College of Pharmacy, Seoul National University) ;
  • Ha, Sang-Jun (System Immunology Laboratory, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University)
  • Received : 2014.07.06
  • Accepted : 2014.08.05
  • Published : 2014.08.31
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Abstract

Chronic virus infection leads to the functional impairment of dendritic cells (DCs) as well as T cells, limiting the clinical usefulness of DC-based therapeutic vaccine against chronic virus infection. Meanwhile, B cells have been known to maintain the ability to differentiate plasma cells producing antibodies even during chronic virus infection. Previously, ${\alpha}$-galactosylceramide (${\alpha}GC$) and cognate peptide-loaded B cells were comparable to DCs in priming peptide-specific $CD8^+$ T cells as antigen presenting cells (APCs). Here, we investigated whether B cells activated by ${\alpha}GC$ can improve virus-specific T cell immune responses instead of DCs during chronic virus infection. We found that comparable to B cells isolated from naïve mice, chronic B cells isolated from chronically infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) after ${\alpha}GC$-loading could activate CD1d-restricted invariant natural killer T (iNKT) cells to produce effector cytokines and upregulate co-stimulatory molecules in both naïve and chronically infected mice. Similar to naïve B cells, chronic B cells efficiently primed LCMV glycoprotein (GP) 33-41-specific P14 $CD8^+$ T cells in vivo, thereby allowing the proliferation of functional $CD8^+$ T cells. Importantly, when ${\alpha}GC$ and cognate epitope-loaded chronic B cells were transferred into chronically infected mice, the mice showed a significant increase in the population of epitope-specific $CD8^+$ T cells and the accelerated control of viremia. Therefore, our studies demonstrate that reciprocal activation between ${\alpha}GC$-loaded chronic B cells and iNKT cells can strengthen virus-specific T cell immune responses, providing an effective regimen of autologous B cell-based therapeutic vaccine to treat chronic virus infection.

Keywords

References

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