• Title/Summary/Keyword: T cell exhaustion

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Interleukin-2 production and alteration of T cell subsets in mice infected with Naegleria fowleri (Naegleria fowleri 감염 마우스에 있어서 interleukin-2 생성 및 T 림프구 아형변동)

  • Yu, Cheol-Ju;Sin, Ju-Ok;Im, Gyeong-Il
    • Parasites, Hosts and Diseases
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    • v.31 no.3
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    • pp.249-258
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    • 1993
  • Naegleria fowleri is the cause of primary amoebic meningoencephalitis in man, IL-2 levels after stimulation of T lymphocytes by PHA or N.fowleri lysates. the amounts of T lymphocyte subsets and the blastogenic responses of T lymphocytes in mice after Infected with pathogenic N. fowleri were studied comparing between two study groups, one $1{\;}{\times}{\;}10^4$ trophozoites inoculated mice and the other $1{\;}{\times}{\;}10^5$ trophozoites inoculated mice. All experimental samples were obtained on the day 7, 14 and 24 after inoculation. The mice inoculated with $1{\;}{\times}{\;}10^4$ trophozoites showed a 14.3% mortality rate, and 72.2% in the mice inoculated with $1{\;}{\times}{\;}10^5$ trophozoites. The IL-2 levels on day 14 of two experimental groups were significantly decreased as compared with the control group. Thy 1.2+T cells in the total spleen Iymphocytes of $1{\;}{\times}{\;}10^5$ trophozoites inoculated group on day 7 were significantly increased compared with the control group. There was no significant difference between $1{\;}{\times}{\;}10^4$ trophozoites inoculated group and the control group. $L3T4^{+}{\;}T$ cells and $Ly2^{+}$ T cells in the total spleen Iymphocytes of $1{\;}{\times}{\;}10^5$ trophozoites inoculated group on day 7 were sigrlificantly increased compared with the control group. The DNA S fraction of T cells in the spleen of $1{\;}{\times}{\;}10^5$ trophozoites inoculated group was significantly increased on day 7. The amount of S fractions of DNA were sequentially decreased on day 14 and 24 but they were also signiacantly increased compared with the control group. The results obtained in the experiments indicats that cell mediated immunity after N.fowleri infection acts on very important host's protection immunity around the 7th day after infection. IL-2 level was much suppressed on day 14 which resulted from the exhaustion of host immune response. It was observed that the level of IL-2 production ability and the amounts of T lymphocytes subsets and the blastogenic responses of T lymphocytes were not well correlated during the observation period.

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Differential Expression of Th1- and Th2- Type Cytokines in Peripheral Blood Mononuclear Cells of Murrah Buffalo (Bubalus Bubalis) on TLR2 Induction by B. Subtilis Peptidoglycan

  • Shah, Syed M.;Ravi Kumar, G.V.P.P.S.;Brah, G.S.;Santra, Lakshman;Pawar, Hitesh
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.7
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    • pp.1021-1028
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    • 2012
  • Peripheral blood mononuclear cells (PBMCs) discriminate microbial pathogens and induce T-cell responses of appropriate effector phenotype accordingly. Toll-like receptors (TLRs), in part, mediate this microbial recognition and differentiation while the development of T-cell effector functions critically depends on the release of Th1- or Th2- type cytokines. In the present study, buffalo PBMCs were stimulated under in vitro culture conditions by Bacillus subtilis cell wall petidoglycan, a TLR2 ligand, in a dose- and time- dependent manner. The expression of TLR2 as well as the subsequent differential induction of the Th1 and Th2 type cytokines was measured. Stimulation was analyzed across five doses of peptidoglycan ($10{\mu}g/ml$, $20{\mu}g/ml$, $30{\mu}g/ml$, $40{\mu}g/ml$ and $50{\mu}g/ml$) for 3 h, 12 h, 24 h and 36 h incubation periods. We observed the induction of TLR2 expression in a dose- and time-dependent manner and the peptidoglycan induced tolerance beyond $30{\mu}g/ml$ dose at all incubation periods. The correlation between peptidoglycan stimulation and TLR2 induction was found positive at all doses and for all incubation periods. Increased production of all the cytokines was observed at low doses for 3 h incubation, but the expression of IL-4 was relatively higher than IL-12 at the higher antigen doses, indicating tailoring towards Th2 response. At 12 h incubation, there was a pronounced decrease in IL-4 and IL-10 expression relative to IL-12 in a dose- dependent manner, indicating skewing to Th1 polarization. The expression of IL-12 was highest for all doses across all the incubation intervals at 24 h incubation, indicating Th1 polarization. The relative expression of TNF-${\alpha}$ and IFN-${\gamma}$ was also higher while that of IL-4 and IL-10 showed a decrease. For 36 h incubation, at low doses, relative increase in the expression of IL-4 and IL-10 was observed which decreased at higher doses, as did the expression of all other cytokines. The exhaustion of cytokine production at 36 h indicated that PBMCs became refractory to further stimulation. It can be concluded from this study that the cytokine response to sPGN initially was of Th2 type which skews, more pronouncedly, to Th1 type with time till the cells become refractory to further stimulation.

The Optimal Activation State of Dendritic Cells for the Induction of Antitumor Immunity (항종양 면역반응 유도를 위한 수지상세포의 최적 활성화 조건)

  • Nam, Byung-Hyouk;Jo, Wool-Soon;Lee, Ki-Won;Oh, Su-Jung;Kang, Eun-Young;Choi, Yu-Jin;Do, Eun-Ju;Hong, Sook-Hee;Lim, Young-Jin;Kim, Ki-Uk;Jeong, Min-Ho
    • Journal of Life Science
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    • v.16 no.6
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    • pp.904-910
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    • 2006
  • Dendritic cells (DCs) are the only antigen presenting cells (APCs) capable of initiating immune responses, which is crucial for priming the specific cytotoxic T lymphocyte (CTL) response and tumor immunity. Upon activation by DCs, CD4+ helper T cells can cross-prime CD8+ CTLs via IL-12. However, recently activated DCs were described to prime in vitro strong T helper cell type 1 $(Th_1)$ responses, whereas at later time points, they preferentially prime $Th_2$ cells. Therfore, we examined in this study the optimum kinetic state of DCs activation impacted on in vivo priming of tumor-specific CTLs by using ovalbumin (OVA) tumor antigen model. Bone-marrow-derived DCs showed an appropriate expression of surface MHC and costimulatory molecules after 6 or 7-day differentiation. The 6-day differentiated DCs pulsed with OVA antigen for 8 h (8-h DC) and followed by restimulation with LPS for 24 h maintained high interleukin (IL)-12 production potential, accompanying the decreased level in their secretion by delayed re-exposure time to LPS. Furthermore, immunization with 8-h DC induced higher intracellular $interferon(IFN)-{\gamma}+/CD8+T$ cells and elicited more powerful cytotoxicity of splenocytes to EG7 cells, a clone of EL4 cells transfected with an OVA cDNA, than immunization with 24-h DC. In the animal study for the evaluation of therapeutic or protective antitumor immunity, immunization with 8-h DC induced an effective antitumor immunity against tumor of EG7 cells and completely protected mice from tumor formation and prolonged survival, respectively. The most commonly used and clinically applied DC-based vaccine is based on in vitro antigen loading for 24 h. However, our data indicated that antigen stimulation over 8 h decreased antitumor immunity with functional exhaustion of DCs, and that the 8-h DC would be an optimum activation state impacted on in vivo priming of tumor-specific CTLs and subsequently lead to induction of strong antitumor immunity.

Optimization of DME Reforming using Steam Plasma (수증기 플라즈마를 이용한 DME 개질의 최적화 방안 연구)

  • Jung, Kyeongsoo;Chae, U-Ri;Chae, Ho Keun;Chung, Myeong-Sug;Lee, Joo-Yeoun
    • Journal of Korea Society of Industrial Information Systems
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    • v.24 no.5
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    • pp.9-16
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    • 2019
  • In today's global energy market, the importance of green energy is emerging. Hydrogen energy is the future clean energy source and one of the pollution-free energy sources. In particular, the fuel cell method using hydrogen enhances the flexibility of renewable energy and enables energy storage and conversion for a long time. Therefore, it is considered to be a solution that can solve environmental problems caused by the use of fossil resources and energy problems caused by exhaustion of resources simultaneously. The purpose of this study is to efficiently produce hydrogen using plasma, and to study the optimization of DME reforming by checking the reforming reaction and yield according to temperature. The research method uses a 2.45 GHz electromagnetic plasma torch to produce hydrogen by reforming DME(Di Methyl Ether), a clean fuel. Gasification analysis was performed under low temperature conditions ($T3=1100^{\circ}C$), low temperature peroxygen conditions ($T3=1100^{\circ}C$), and high temperature conditions ($T3=1376^{\circ}C$). The low temperature gasification analysis showed that methane is generated due to unstable reforming reaction near $1100^{\circ}C$. The low temperature peroxygen gasification analysis showed less hydrogen but more carbon dioxide than the low temperature gasification analysis. Gasification analysis at high temperature indicated that methane was generated from about $1150^{\circ}C$, but it was not generated above $1200^{\circ}C$. In conclusion, the higher the temperature during the reforming reaction, the higher the proportion of hydrogen, but the higher the proportion of CO. However, it was confirmed that the problem of heat loss and reforming occurred due to the structural problem of the gasifier. In future developments, there is a need to reduce incomplete combustion by improving gasifiers to obtain high yields of hydrogen and to reduce the generation of gases such as carbon monoxide and methane. The optimization plan to produce hydrogen by steam plasma reforming of DME proposed in this study is expected to make a meaningful contribution to producing eco-friendly and renewable energy in the future.