Enhancing T Cell Immune Responses by B Cell-based Therapeutic Vaccine Against Chronic Virus Infection.
- Author:
Min Ki KIM
1
;
Ara LEE
;
Yu Kyeong HWANG
;
Chang Yuil KANG
;
Sang Jun HA
Author Information
- Publication Type:Original Article
- Keywords: Chronic virus infection; B-cell based therapeutic vaccine; alpha-galactosylceramide; T cell immune responses
- MeSH: Animals; Antibodies; Antigen-Presenting Cells; B-Lymphocytes; Clone Cells; Cytokines; Dendritic Cells; Glycoproteins; Lymphocytic choriomeningitis virus; Mice; Natural Killer T-Cells; Plasma Cells; T-Lymphocytes; Viremia
- From:Immune Network 2014;14(4):207-218
- CountryRepublic of Korea
- Language:English
- 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 (alphaGC) 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 alphaGC can improve virus-specific T cell immune responses instead of DCs during chronic virus infection. We found that comparable to B cells isolated from naive mice, chronic B cells isolated from chronically infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) after alphaGC-loading could activate CD1d-restricted invariant natural killer T (iNKT) cells to produce effector cytokines and upregulate co-stimulatory molecules in both naive and chronically infected mice. Similar to naive 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 alphaGC 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 alphaGC-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.
