DNA vaccine using hemagglutinating virus of Japan-liposome encapsulating combination encoding mycobacterial heat shock protein 65 and interleukin-12 confers protection against Mycobacterium tuberculosis by T cell activation

Vaccine ◽  
2006 ◽  
Vol 24 (8) ◽  
pp. 1191-1204 ◽  
Author(s):  
S YOSHIDA ◽  
T TANAKA ◽  
Y KITA ◽  
S KUWAYAMA ◽  
N KANAMARU ◽  
...  
2005 ◽  
Vol 65 (9) ◽  
pp. 3942-3949 ◽  
Author(s):  
Lorenzo Pilla ◽  
Paola Squarcina ◽  
Jorgelina Coppa ◽  
Vincenzo Mazzaferro ◽  
Veronica Huber ◽  
...  

2009 ◽  
Vol 390 (4) ◽  
Author(s):  
Maya J. Pandya ◽  
Henriette Bendz ◽  
Florian Manzenrieder ◽  
Elfriede Noessner ◽  
Horst Kessler ◽  
...  

Abstract Molecular chaperones of the heat shock protein 70 (Hsp70) family play a crucial role in the presentation of exogenous antigenic peptides by antigen-presenting cells (APCs). In a combined biochemical and immunological approach, we characterize the biochemical interaction of tumor-associated peptides with human Hsp70 and show that the strength of this interaction determines the efficacy of immunological cross-presentation of the antigenic sequences by APCs. A fluorescein-labeled cytosolic mammalian Hsc70 binding peptide is shown to interact with human Hsp70 molecules with high affinity (Kd=0.58 μm at 25°C). Competition experiments demonstrate weaker binding by Hsp70 of antigenic peptides derived from the tumor-associated proteins tyrosinase (Kd=32 μm) and melanoma antigen recognized by T cells (MART-1) (Kd=2.4 μm). Adding a peptide sequence (pep70) with high Hsp70 binding affinity (Kd=0.04 μm) to the tumor-associated peptides enables them to strongly interact with Hsp70. Presentation of tumor-associated peptides by B cells resulting in T cell activation in vitro is enhanced by Hsp70 when the tumor-associated peptides contain the Hsp70 binding sequence. This observation has relevance for vaccine design, as augmented transfer of tumor-associated antigens to APCs is closely linked to the vaccine's efficacy of T cell stimulation.


2009 ◽  
Vol 183 (5) ◽  
pp. 3092-3098 ◽  
Author(s):  
Jianlin Gong ◽  
Bangmin Zhu ◽  
Ayesha Murshid ◽  
Hideki Adachi ◽  
Baizheng Song ◽  
...  

2011 ◽  
Vol 151 (4) ◽  
pp. 343-349 ◽  
Author(s):  
Yang Li ◽  
Haolei Song ◽  
Jin Li ◽  
Yanzhong Wang ◽  
Xiaoli Yan ◽  
...  

2013 ◽  
Vol 21 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Tetsu Mukai ◽  
Yumiko Tsukamoto ◽  
Yumi Maeda ◽  
Toshiki Tamura ◽  
Masahiko Makino

ABSTRACTFor the purpose of obtainingMycobacterium bovisbacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed ofMycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8+T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8+T cells and perforin-producing effector CD8+T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive toin vitrosecondary stimulation with HSP70, MMP-II, andM. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challengedM. tuberculosismore efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.


2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Song Chen ◽  
Ran Ding ◽  
Yan Zhou ◽  
Xian Zhang ◽  
Rui Zhu ◽  
...  

YCP, as a kind of natural polysaccharides from the mycelium of marine filamentous fungusPhoma herbarumYS4108, has great antitumor potentialviaenhancement of host immune response, but little is known about the molecular mechanisms. In the present study, we mainly focused on the effects and mechanisms of YCP on the specific immunity mediated by dendritic cells (DCs) and T cells. T cell /DC activation-related factors including interferon- (IFN-)γ, interleukin-12 (IL-12), and IL-4 were examined with ELISA. Receptor knock-out mice and fluorescence-activated cell sorting are used to analyze the YCP-binding receptor of T cells and DCs. RT-PCR is utilized to measure MAGE-A3 for analyzing the tumor-specific killing effect. In our study, we demonstrated YCP can provide the second signal for T cell activation, proliferation, and IFN-γproduction through binding to toll-like receptor- (TLR-) 2 and TLR-4. YCP could effectively promote IL-12 secretion and expression of markers (CD80, CD86, and MHC II)viaTLR-4 on DCs. Antigen-specific immunity against mouse melanoma cells was strengthened through the activation of T cells and the enhancement of capacity of DCs by YCP. The data supported that YCP can exhibit specific immunomodulatory capacity mediated by T cells and DCs.


2011 ◽  
Vol 49 (1) ◽  
pp. 85 ◽  
Author(s):  
Hyo-Jin Kim ◽  
Bong-Kwang Jung ◽  
Jin-Joo Lee ◽  
Kyoung-Ho Pyo ◽  
Tae Yun Kim ◽  
...  

1999 ◽  
Vol 190 (9) ◽  
pp. 1275-1284 ◽  
Author(s):  
Leo Lefrançois ◽  
Sara Olson ◽  
David Masopust

The role of CD40 ligand (CD40L) in CD8 T cell activation was assessed by tracking antigen-specific T cells in vivo using both adoptive transfer of T cell receptor transgenic T cells and major histocompatibility complex (MHC) class I tetramers. Soluble antigen immunization induced entry of CD8 cells into the intestinal mucosa and cytotoxic T lymphocyte (CTL) differentiation, whereas CD8 cells in secondary lymphoid tissue proliferated but were not cytolytic. Immunization concurrent with CD40L blockade or in the absence of CD40 demonstrated that accumulation of CD8 T cells in the mucosa was CD40L dependent. Furthermore, activation was mediated through CD40L expressed by the CD8 cells, since inhibition by anti-CD40L monoclonal antibodies occurred after adoptive transfer to CD40L-deficient mice. However, mucosal CD8 T cells in normal and CD40−/− mice were equivalent killers, indicating that CD40L was not required for CTL differentiation. Appearance of virus-specific mucosal, but not splenic, CD8 cells also relied heavily on CD40–CD40L interactions. The mucosal CTL response of transferred CD8 T cells was MHC class II and interleukin 12 independent. The results established a novel pathway of direct CD40L-mediated CD8 T cell activation.


1997 ◽  
Vol 186 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Andrea M. Cooper ◽  
Jeanne Magram ◽  
Jessica Ferrante ◽  
Ian M. Orme

Immunity to Mycobacterium tuberculosis infection is associated with the emergence of protective CD4 T cells that secrete cytokines, resulting in activation of macrophages and the recruitment of monocytes to initiate granuloma formation. The cytokine-mediating macrophage activation is interferon-γ (IFN-γ), which is largely dependent on interleukin-12 (IL-12) for its induction. To address the role of IL-12 in immunity to tuberculosis, IL-12 p40−/− mice were infected with M. tuberculosis and their capacity to control bacterial growth and other characteristics of their immune response were determined. The IL-12 p40−/− mice were unable to control bacterial growth and this appeared to be linked to the absence of both innate and acquired sources of IFN-γ. T cell activation as measured by delayed type hypersensitivity and lymphocyte accumulation at the site of infection were both markedly reduced in the IL-12 p40−/− mice. Therefore, IL-12 is essential to the generation of a protective immune response to M. tuberculosis, with its main functions being the induction of the expression of IFN-γ and the activation of antigen-specific lymphocytes capable of creating a protective granuloma.


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