• Title/Summary/Keyword: T cell immunity

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Perspectives of AIDS Vaccine Development: T Cell-based Vaccine

  • Sung, Young Chul
    • IMMUNE NETWORK
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    • v.2 no.1
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    • pp.1-5
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    • 2002
  • Estimated number of adults and children newly infected with HIV-1 during 2001 alone is 5 million in total. An effective vaccine, in addition to education & public health approaches, has been believed to be the best option to stop the HIV-1 transmission, especially for developing countries. Among AIDS vaccine candidates, DNA vaccine is relatively safe and, in a certain extent, mimics some attributes of live attenuated vaccine, with regard to in vivo gene expression & the type of immunity induced. We recently demonstrated that DNA vaccines expressing SIVmac239 structural and regulatory genes, augmented with coadministration of IL-12 mutant induced the strongest T cell responses, resulting in low to undetectable setpoint viral loads, stable $CD4^+$ T cell counts, and no evidence of clinical diseases or mortality by day 420 after challenge. This finding is the second demonstration, following the protective result of live attenuated SIV vaccine in SIVmac-rhesus monkey model, which was known to have safety problem. So, our DNA vaccines could give a significant impact on HIV-1 epidemic by slowing or stopping the spread of HIV-1, leading to eventual eradication of HIV-1 and AIDS in the population.

Increased Frequency of Foxp3+ Regulatory T Cells in Mice with Hepatocellular Carcinoma

  • Du, Yong;Chen, Xin;Huang, Zhi-Ming;Ye, Xiao-Hua;Niu, Qing
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3815-3819
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    • 2012
  • The CD4+CD25+ regulatory T cell (Treg) is a special kind of T cell subset. Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer. Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance. The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma (HCC). A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods. Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status.The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ($18.8%{\pm}1.26%$) was found to be significantly higher than that in normal mice ($9.99%{\pm}1.90%$) (P<0.01 ). Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed. Anti-tumour immunity was suppressed, and this might be associated with the increase of Tregs. Our observations suggest that the CD4+CD25+Treg/CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer.

CD137-CD137 Ligand Interactions in Inflammation

  • Kwon, Byung-Suk
    • IMMUNE NETWORK
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    • v.9 no.3
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    • pp.84-89
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    • 2009
  • The main stream of CD137 studies has been directed to the function of CD137 in $CD8^+$ T-cell immunity, including its anti-tumor activity, and paradoxically the immunosuppressive activity of CD137, which proves to be of a great therapeutic potential for animal models of a variety of autoimmune and inflammatory diseases. Recent studies, however, add complexes to the biology of CD137. Accumulating is evidence supporting that there exists a bidirectional signal transduction pathway for the CD137 receptor and its ligand (CD137L). CD137/CD137L interactions are involved in the network of hematopoietic and nonhematopoietic cells in addition to the well characterized antigen-presenting cell-T cell interactions. Signaling through CD137L plays a critical role in the differentiation of myeloid cells and their cellular activities, suggesting that CD137L signals trigger and sustain inflammation. The overall consequence might be that the amplified inflammation by CD137L enhances the T-cell activity together with CD137 signals by upregulating costimulatory molecules, MHC molecules, cell adhesion molecules, cytokines, and chemokines. Solving this outstanding issue is urgent and will have an important clinical implication.

Ralstonia solanacearum Type III Effectors with Predicted Nuclear Localization Signal Localize to Various Cell Compartments and Modulate Immune Responses in Nicotiana spp.

  • Jeon, Hyelim;Kim, Wanhui;Kim, Boyoung;Lee, Sookyeong;Jayaraman, Jay;Jung, Gayoung;Choi, Sera;Sohn, Kee Hoon;Segonzac, Cecile
    • The Plant Pathology Journal
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    • v.36 no.1
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    • pp.43-53
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    • 2020
  • Ralstonia solanacearum (Rso) is a causal agent of bacterial wilt in Solanaceae crops worldwide including Republic of Korea. Rso virulence predominantly relies on type III secreted effectors (T3Es). However, only a handful of Rso T3Es have been characterized. In this study, we investigated subcellular localization of and manipulation of plant immunity by 8 Rso T3Es predicted to harbor a nuclear localization signal (NLS). While 2 of these T3Es elicited cell death in both Nicotiana benthamiana and N. tabacum, only one was dependent on suppressor of G2 allele of skp1 (SGT1), a molecular chaperone of nucleotide-binding and leucine-rich repeat immune receptors. We also identified T3Es that differentially regulate flg22-induced reactive oxygen species production and gene expression. Interestingly, several of the NLS-containing T3Es translationally fused with yellow fluorescent protein accumulated in subcellular compartments other than the cell nucleus. Our findings bring new clues to decipher Rso T3E function in planta.

Common and differential effects of docosahexaenoic acid and eicosapentaenoic acid on helper T-cell responses and associated pathways

  • Lee, Jaeho;Choi, Yu Ri;Kim, Miso;Park, Jung Mi;Kang, Moonjong;Oh, Jaewon;Lee, Chan Joo;Park, Sungha;Kang, Seok-Min;Manabe, Ichiro;Ann, Soo-jin;Lee, Sang-Hak
    • BMB Reports
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    • v.54 no.5
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    • pp.278-283
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    • 2021
  • Our understanding of the differential effects between specific omega-3 fatty acids is incomplete. Here, we aimed to evaluate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on T-helper type 1 (Th1) cell responses and identify the pathways associated with these responses. Naïve CD4+ T cells were co-cultured with bone marrow-derived dendritic cells (DCs) in the presence or absence of palmitate (PA), DHA, or EPA. DHA or EPA treatment lowered the number of differentiated IFN-γ-positive cells and inhibited the secretion of IFN-γ, whereas only DHA increased IL-2 and reduced TNF-α secretion. There was reduced expression of MHC II on DCs after DHA or EPA treatment. In the DC-independent model, DHA and EPA reduced Th1 cell differentiation and lowered the cell number. DHA and EPA markedly inhibited IFN-γ secretion, while only EPA reduced TNF-α secretion. Microarray analysis identified pathways involved in inflammation, immunity, metabolism, and cell proliferation. Moreover, DHA and EPA inhibited Th1 cells through the regulation of diverse pathways and genes, including Igf1 and Cpt1a. Our results showed that DHA and EPA had largely comparable inhibitory effects on Th1 cell differentiation. However, each of the fatty acids also had distinct effects on specific cytokine secretion, particularly according to the presence of DCs.

Effect of Lipofectin on Antigen-presenting Function and Anti-tumor Activity of Dendritic Cells (수지상세포의 항원제시 능력 및 항암활성에 미치는 Lipofectin의 영향)

  • Noh, Young-Woock;Lim, Jong-Seok
    • IMMUNE NETWORK
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    • v.6 no.2
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    • pp.102-110
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    • 2006
  • Background: Dendritic cells (DC) are professional antigen-presenting cells in the immune system and can induce T cell response against virus infections, microbial pathogens, and tumors. Therefore, immunization using DC loaded with tumor-associated antigens (TAAs) is a powerful method of inducing anti-tumor immunity. For induction of effective anti-tumor immunity, antigens should be efficiently introduced into DC and presented on MHC class I molecules at high levels to activate antigen-specific $CD8^+$ T cells. We have been exploring methods for loading exogenous antigens into APC with high efficiency of Ag presentation. In this study, we tested the effect of the cationic liposome (Lipofectin) for transferring and loading exogenous model antigen (OVA protein) into BM-DC. Methods: Bone marrow-derived DC (EM-DC) were incubated with OVA-Lipofectin complexes and then co-cultured with B3Z cells. B3Z activation, which is expressed as the amount of ${\beta}$-galactosidase induced by TCR stimulation, was determined by an enzymatic assay using ${\beta}$-gal assay system. C57BL/6 mice were immunized with OVA-pulsed DC to monitor the in vivo vaccination effect. After vaccination, mice were inoculated with EG7-OVA tumor cells. Results: BM-DC pulsed with OVA-Lipofectin complexes showed more efficient presentation of OVA-peptide on MHC class I molecules than soluble OVA-pulsed DC. OVA-Lipofectin complexes-pulsed DC pretreated with an inhibitor of MHC class I-mediated antigen presentation, brefeldin A, showed reduced ability in presenting OVA peptide on their surface MHC class I molecules. Finally, immunization of OVA-Lipofectin complexes-pulsed DC protected mice against subsequent tumor challenge. Conclusion: Our data provide evidence that antigen-loading into DC using Lipofectin can promote MHC class I- restricted antigen presentation. Therefore, antigen-loading into DC using Lipofectin can be one of several useful tools for achieving efficient induction of antigen-specific immunity in DC-based immunotherapy.

Intranasal Immunization With Nanoparticles Containing an Orientia tsutsugamushi Protein Vaccine Candidate and a Polysorbitol Transporter Adjuvant Enhances Both Humoral and Cellular Immune Responses

  • Cheol Gyun Kim;Won Kyong Kim;Narae Kim;Young Jin Pyung;Da-Jeong Park;Jeong-Cheol Lee;Chong-Su Cho;Hyuk Chu;Cheol-Heui Yun
    • IMMUNE NETWORK
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    • v.23 no.6
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    • pp.47.1-47.16
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    • 2023
  • Scrub typhus, a mite-borne infectious disease, is caused by Orientia tsutsugamushi. Despite many attempts to develop a protective strategy, an effective preventive vaccine has not been developed. The identification of appropriate Ags that cover diverse antigenic strains and provide long-lasting immunity is a fundamental challenge in the development of a scrub typhus vaccine. We investigated whether this limitation could be overcome by harnessing the nanoparticle-forming polysorbitol transporter (PST) for an O. tsutsugamushi vaccine strategy. Two target proteins, 56-kDa type-specific Ag (TSA56) and surface cell Ag A (ScaA) were used as vaccine candidates. PST formed stable nano-size complexes with TSA56 (TSA56-PST) and ScaA (ScaA-PST); neither exhibited cytotoxicity. The formation of Ag-specific IgG2a, IgG2b, and IgA in mice was enhanced by intranasal vaccination with TSA56-PST or ScaA-PST. The vaccines containing PST induced Ag-specific proliferation of CD8+ and CD4+ T cells. Furthermore, the vaccines containing PST improved the mouse survival against O. tsutsugamushi infection. Collectively, the present study indicated that PST could enhance both Ag-specific humoral immunity and T cell response, which are essential to effectively confer protective immunity against O. tsutsugamushi infection. These findings suggest that PST has potential for use in an intranasal vaccination strategy.

A literature study on oncological Immune therapy (암(癌)의 면역치료(免疫治療)에 대(對)한 고찰(考察))

  • Park, Jong-Hak;Son, Chang-Gyu;Cho, Chong-kwan
    • Journal of Haehwa Medicine
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    • v.9 no.2
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    • pp.211-221
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    • 2001
  • A literature study on oncological immune therapy was done, and the results were as follows. 1. Oncological immune therapy is classified as specific non specific therapy or active inactive therapy, and in tumor immune response, cellular immunity operates mainly, so activity of T lymphocytes and macrophages are closely related with growth, progress, metastasis and prospect of tumor. Recently, Immune therapies of gene which use cytokines and HLA-B7 are carrying out. 2. In oriental medicine, development of disease is closely related to up and down of healthy qi, so healthy qi operates as a immune factor and resistance factor. 3. On the base of theory "Increasing healthy qi reduces mass(養正則積自除)", strengthening body resistance is emphasized in cancer therapy. Also strengthening body resistance activates cellular immune response and promote killing tumor facility of T-cell. 4. In clinical view, using immune therapy after operation, radiation, and chemotheraphy is more effective than immune therapy itself, so it is expected that east-west cooperation will be effective in cancer therapy. 5. The study of oncological immunity is progressed on emphasizing T-cell and it is related to oriental medical theory "strengthening healthy qi to eliminate pathogen(扶定祛邪)" and advanced study is expected in future.

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The effect of active immunization with Acanthamoebn culbeksoni in mice born to immune mother (수동면역이 Acanthmoeba culbertsoni 능동면역 형성에 미치는 영향)

  • 공현호;서성아
    • Parasites, Hosts and Diseases
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    • v.31 no.2
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    • pp.157-164
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    • 1993
  • Acanthamoebn culbertsoni is a pathogenic free-living amoeba causing primary amoebic meningoencephalltls (PAME) in human and mouse. Several reports on the immune responses in mice with this amoebic infection have been published, but the effects of transferred passive Immunity on the active immunization In offspring mice have not been demonstrated. This experiment was done to observe the effect of active Acanthamoebn culbertsoni was cultured in the CGV medium axenlcally. Female BALB/c mice weighing about 20g were immunized through the intraperitoneal injection of Acanthamoeba cuLbensoni trophozoites 1 × 106 each three times at the interval of one week. Offspring mice were immunized two times. The mice were inoculated Intranasally with 1 × 104 trophozoites under secobarbital anesthesia. There was a statistical difference in mortality between the transferred immunity group and the active immunization group. Statistical differences were not demonstrated in antibody titer between both groups. But L3T4+ T ce11/Ly2+T cell ratio was increased in the transferred Immunity group more than active immunization group of the offspring mice at the age of 5 weeks. There was no differences statistically in mortality between both groups. It was recognized that active immunization in offspring mice born to immune mother could modulate the immune status according to the time of Immunization.

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DW2007 Ameliorates Colitis and Rheumatoid Arthritis in Mice by Correcting Th17/Treg Imbalance and Inhibiting NF-κB Activation

  • Lim, Su-Min;Lee, Sang-Yun;Jeong, Jin-Ju;Choi, Hyun Sik;Chang, Hwan Bong;Kim, Dong-Hyun
    • Biomolecules & Therapeutics
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    • v.24 no.6
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    • pp.638-649
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    • 2016
  • In the previous study, the rhizome mixture of Anemarrhena asphodeloides and Coptis chinensis (DW2007), improved TNBS-, oxazolone-, or DSS-induced colitis in mice by regulating macrophage activation. Therefore, to understand the effect of DW2007 on the T cell differentiation involved in the adaptive immunity, we measured its effect on both Th17 and Treg cell differentiation in splenocytes, in the lamina propria of mice with DSS-induced colitis (DIC), and in the spleens of mice with collagen-induced arthritis (CIA). Results showed that DW2007 potently inhibited the differentiation of splenocytes into Th17 cells, but increased Treg cell differentiation in vitro. In the colon of wild type and $TLR4^{-/-}$ mice with DIC, DW2007 potently suppressed DSS-induced colon shortening and myeloperoxidase activity. DW2007 also suppressed collagen-induced paw thickening, clinical index, and myeloperoxidase activity in CIA mice. Overall, DW2007 potently suppressed Th17 cell differentiation in mice with CIA and DIC, but increased Treg cell differentiation. Moreover, DW2007 strongly inhibited the expression of TNF-${\alpha}$ and IL-$1{\beta}$, as well as the activation of NF-${\kappa}B$. Based on these findings, DW2007 may ameliorate inflammatory diseases by regulating the innate immunity via the inhibition of macrophage activation and the adaptive immunity via the correction of disturbed Th17/Treg cells.