|
KMID : 0923620140140040207
|
|
Immune Network
2014 Volume.14 No. 4 p.207 ~ p.218
|
|
|
Enhancing T Cell Immune Responses by B Cell-based Therapeutic Vaccine Against Chronic Virus Infection
|
|
Kim Min-Ki
Lee A-Ra
Hwang Yu-Kyeong
Kang Chang-Yuil
Ha Sang-Jun
|
|
|
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 main-tain the ability to differentiate plasma cells producing anti-bodies 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 naive mice, chronic B cells isolated from chroni-cally infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) after αGC-loading could activate CD1d-restricted invariant natural killer T (iNKT) cells to pro-duce effector cytokines and upregulate co-stimulatory mole-cules in both naive and chronically infected mice. Similar to naive B cells, chronic B cells efficiently primed LCMV glyco-protein (GP) 33-41-specific P14 CD8＋ T cells in vivo, there-by 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 epit-ope-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.
|
|
|
KEYWORD
|
|
|
Chronic virus infection, B-cell based therapeutic vaccine, α-galactosylceramide, T cell immune responses
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
   
|
|