Enhancing T Cell Immune Responses by B Cell-based Therapeutic Vaccine Against Chronic Virus Infection
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (37)
- Wherry, E. J., "Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment", J. Virol, 77, pp.4911~4927 (2003)
- Ha, S. J, "Manipulating both the inhibitory and stimulatory immune system towards the success of therapeutic vaccination against chronic viral infections", Immunol. Rev, 223, pp.317~333 (2008)
- Virgin, H. W., "Redefining chronic viral infection", Cell, 138, pp.30~50 (2009)
- Zajac, A. J., "Viral immune evasion due to persistence of activated T cells without effector function", J. Exp. Med, 188, pp.2205~2213 (1998)
- Hyun-Tak Jin, "Mechanism of T cell exhaustion in a chronic environment", BMB Reports, 44(4), pp.217~231 (2011), 생화학분자생물학회
- Ng, C. T., "Networking at the level of host immunity : immune cell interactions during persistent viral infections", Cell Host Microbe, 13, pp.652~664 (2013)
- Fahey, L. M, "Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells", J. Exp. Med, 208, pp.987~999 (2011)
- Rosenberg, S. A., "Cancer immunotherapy: moving beyond current vaccines", Nat. Med, 10, pp.909~915 (2004)
- Figdor, C. G., "Dendritic cell immunotherapy: mapping the way", Nat. Med, 10, pp.475~480 (2004)
- Janikashvili, N., "Personalized dendritic cell-based tumor immunotherapy", Immunotherapy, 2, pp.57~68 (2010)
- Schultze, J. L., "DCs and CD40-activated B cells: current and future avenues to cellular cancer immunotherapy", Trends Immunol, 25, pp.659~664 (2004)
- Eynon, E. E., "Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens", J. Exp. Med, 175, pp.131~138 (1992)
- Fuchs, E. J., "B cells turn off virgin but not memory T cells", Science, 258, pp.1156~1159 (1992)
- Schultze, J. L, "CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy", J. Clin. Iinvest, 100, pp.2757~2765 (1997)
- Coughlin, C. M, "RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy", Blood, 103, pp.2046~2054 (2004)
- Lapointe, R., "CD40-stimulated B lymphocytes pulsed with tumor antigens are effective antigen-presenting cells that can generate specific T cells", Cancer Res, 63, pp.2836~2843 (2003)
- Bendelac, A., "The biology of NKT cells", Annu. Rev. Immunol, 25, pp.297~336 (2007)
- Godfrey, D. I, "Raising the NKT cell family", Nat. Immunol, 11, pp.197~206 (2010)
- Kronenberg, M, "Toward an understanding of NKT cell biology: progress and paradoxes", Annu. Rev. Immunol, 23, pp.877~900 (2005)
- Park, S. H., "CD1-restricted T-cell responses and microbial infection", Nature, 406, pp.788~792 (2000)
- Chung, Y., "CD1d-restricted T cells license B cells to generate long-lasting cytotoxic antitumor immunity in vivo", Cancer Res, 66, pp.6843~6850 (2006)
- Godfrey, D. I., "Going both ways: immune regulation via CD1d-dependent NKT cells", J. Clin. Invest, 114, pp.1379~1388 (2004)
- Kim, Y. J., "alpha-Galactosylceramide-loaded, antigen-expressing B cells prime a wide spectrum of antitumor immunity", Int. J. Cancer, 122, pp.2774~2783 (2008)
- Hermans, I. F., "NKT cells enhance CD4＋ and CD8＋ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells", J. Immunol, 171, pp.5140~5147 (2003)
- Stober, D, "NKT cells provide help for dendritic cell-dependent priming of MHC class I-restricted CD8＋ T cells in vivo", J. Immunol, 170, pp.2540~2548 (2003)
- Cerundolo, V, "Harnessing invariant NKT cells in vaccination strategies", Nat. Rev. Immunol, 9, pp.28~38 (2009)
- Ha, S. J, "Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection", J. Exp. Med, 205, pp.543~555 (2008)
- Barber, D. L, "Restoring function in exhausted CD8 T cells during chronic viral infection", Nature, 439, pp.682~687 (2006)
- King, C. C, "In vivo selection of lymphocyte-tropic and macrophage-tropic variants of lymphocytic choriomeningitis virus during persistent infection", J. Virol, 64, pp.5611~5616 (1990)
- Elsaesser, H., "IL-21 is required to control chronic viral infection", Science, 324, pp.1569~1572 (2009)
- Frohlich, "IL-21R on T cells is critical for sustained functionality and control of chronic viral infection", Science, 324, pp.1576~1580 (2009)
- Yi, J. S, "A vital role for interleukin-21 in the control of a chronic viral infection", Science, 324, pp.1572~1576 (2009)
- Linterman, M. A, "IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses", J. Exp. Med, 207, pp.353~363 (2010)
- Zotos, D., "IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism", J. Exp. Med, 207, pp.365~378 (2010)
- Sharpe, A. H, "The B7-CD28 superfamily", Nat. Rev. Immunol, 2, pp.116~126 (2002)
- Wherry, E. J., "Molecular signature of CD8＋ T cell exhaustion during chronic viral infection", Immunity, 27, pp.670~684 (2007)
- Wiesner, M., "Conditional immortalization of human B cells by CD40 ligation", PLoS One, 3, pp.e1464~ (2008)