title: Enhancing T Cell Immune Responses by B Cell-based Therapeutic Vaccine Against Chronic Virus Infection.
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, α-galactosylceramide (αGC) 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 αGC 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 αGC-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 αGC 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 αGC-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.
authors.affiliation: System Immunology Laboratory, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Min Ki
authors.initials: MK
authors.lastname: Kim
authors.affiliation: System Immunology Laboratory, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Lee
authors.affiliation: Cell Therapy Team, Mogam Biotechnology Institute, Yongin 446-799, Korea.
authors.forename: Yu Kyeong
authors.initials: YK
authors.lastname: Hwang
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 110-799, Korea.
authors.forename: Chang-Yuil
authors.initials: CY
authors.lastname: Kang
authors.affiliation: System Immunology Laboratory, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
keywords: B-cell based therapeutic vaccine; Chronic virus infection; T cell immune responses; α-galactosylceramide