• Title/Summary/Keyword: CD8+T cells

Search Result 465, Processing Time 0.023 seconds

Prognostic Significance of CD44v6/v7 in Acute Promyelocytic Leukemia

  • Chen, Ping;Huang, Hui-Fang;Lu, Rong;Wu, Yong;Chen, Yuan-Zhong
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.8
    • /
    • pp.3791-3794
    • /
    • 2012
  • CD44v, especially splice variants containing exon v6, has been shown to be related closely to development of different tumors. High levels of CD44v6/v7 have been reported to be associated with invasiveness and metastasis of many malignancies. The objective of this study was to detect expression of CD44v6-containing variants in patients with acute promyelocytic leukemia (APL) and evaluate the potential of CD44v6/v7 for risk stratification. Reverse transcription polymerase chain reaction (RT-PCR) followed by PCR product purification, ligation into T vectors and positive clone sequencing were used to detect CD44 v6-containing variant isoforms in 23 APL patients. Real-time quantitative PCR of the CD44v6/v7 gene was performed in patients with APL and in NB4 cells that were treated with all-trans retinoic acid (ATRA) or arsenic trioxide ($As_2O_3$). Sequencing results identified four isoforms (CD44v6/v7, CD44v6/v8/v10, CD44v6/v8/v9/v10, and CD44v6/v7/v8/v9/v10) in bone marrow mononuclear cells of 23 patients with APL. The level of CD44v6/v7 in high-risk cases was significantly higher than those with low-risk. Higher levels of CD44v6/v7 were found in three patients with central nervous system relapse than in other patients inthe same risk group. Furthermore, in contrast to ATRA, only $As_2O_3$ could significantly down-regulate CD44v6/v7 expression in NB4 cells. Our data suggest that CD44v6/v7 expression may be a prognostic indicator for APL.

Study on the effect of Aqua-acupuncture solution of Paeonia lactiflora on Collagen-Induced Arthritis of Mouse (적작약약침(赤芍藥藥鍼)이 관절염(關節炎)에 미치는 실험적(實驗的) 연구(硏究))

  • Seong, Eun-Ni;Lee, Byung-Ryul
    • Journal of Acupuncture Research
    • /
    • v.17 no.1
    • /
    • pp.221-250
    • /
    • 2000
  • In order to investigate experimentally that the effect of aqua-acupuncture solution of Paeonia lactiflora on arthritis of mice induced by collagenII, the author performed several experimental items : that is increase, paw thickness, DTH, weight of spleen, hematological change, expression of $CD4^+$, $CD8^+$, $CD19^+$, gene expression of IL-1, IL-6, IL-12, IFN-${\gamma}$, TNF, proliferation of synovial cells and cytotoxicity. The results were obtained as follows; 1. Inhibitory effects of aqua-acupuncture solution of Paeonia lactiflora on arthritis induced by collgenII. 1) In incidence, paw edema, AI and DTH were inhibited as compared with control group. 2) The splenic weight was increased and the number of leukocytes was decreased as compared with control group. 3) The number of $CD4^+$, $CD8^+$ activated cells and surface-receptor expression were increased as compared with control group. 4) In hematological change, total protein, creatinine and LDH were decreased significantiy as compared with control group. 2. FACS analysis on normal BABL/c of spenic cells treated with aqua-acupuncture solution of Paeonia lactiflora. 1) Aqua-acupuncture solution of Paeonia lactiflora activated adhesive splenic cells of mice morphologically in vitro. 2) Aqua-acupuncture solution of Paeonia dactiflora enhanced the gene expression of IL-12 and also enhanced that of interferon-${\gamma}$ remarkably. 3) Aqua-acupuncture solution of Paeonia lactiflora reduced the number of $CD4^+$, $CD8^+$, $CD19^+$ activated cells and their surface-receptor expression as compared with control group. 3. Effects of aqua-acupuncture solution of Paeonia lactiflora on human synovial cells. 1) In cytotoxicity against synovial cells, aqua-acupuncture solution of Paeonia lactiflora didn't show cytotoxicity at concentration of $10-100{\mu}g/m{\ell}$ but showed significantly at concentration of $200-400{\mu}g/m{\ell}$ as compared with control group. 2) Aqua-acupuncture solution of Paeonia lactiflora reduced the gene expression of IL-6, IL-$1{\beta}$ and TNF-${\alpha}$. 3) Aqua-acupuncture solution of Paeonia lactiflora inhibited proliferation of synovial cells at concentration of 100 and $200{\mu}g/m{\ell}$.

  • PDF

IL-17-Producing Cells in Tumor Immunity: Friends or Foes?

  • Da-Sol Kuen;Byung-Seok Kim;Yeonseok Chung
    • IMMUNE NETWORK
    • /
    • v.20 no.1
    • /
    • pp.6.1-6.20
    • /
    • 2020
  • IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8+ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

Inhibition of caspase-1-dependent apoptosis suppresses peste des petits ruminants virus replication

  • Lingxia Li;Shengqing Li;Shengyi Han;Pengfei Li;Guoyu Du;Jinyan Wu;Xiaoan Cao;Youjun Shang
    • Journal of Veterinary Science
    • /
    • v.24 no.5
    • /
    • pp.55.1-55.12
    • /
    • 2023
  • Background: Peste des petits ruminants (PPR), caused by the PPR virus (PPRV), is an acute and fatal contagious disease that mainly infects goats, sheep, and other artiodactyls. Peripheral blood mononuclear cells (PBMCs) are considered the primary innate immune cells. Objectives: PBMCs derived from goats were infected with PPRV and analyzed to detect the relationship between PPRV replication and apoptosis or the inflammatory response. Methods: Quantitative real-time polymerase chain reaction was used to identify PPRV replication and cytokines expression. Flow cytometry was conducted to detect apoptosis and the differentiation of CD4+ and CD8+ T cells after PPRV infection. Results: PPRV stimulated the differentiation of CD4+ and CD8+ T cells. In addition, PPRV induced apoptosis in goat PBMCs. Furthermore, apoptosis and the inflammatory response induced by PPRV could be suppressed by Z-VAD-FMK and Z-YVAD-FMK, respectively. Moreover, the virus titer of PPRV was attenuated by inhibiting caspase-1-dependent apoptosis and inflammation. Conclusions: This study showed that apoptosis and the inflammatory response play an essential role in PPR viral replication in vitro, providing a new mechanism related to the cell host response.

Protective Effects on A2Kb Transgenic Mice That Were Immunized with Hepatitis B Virus X Antigen Peptides by the Activation of CD8+ T Cells; XEP-3 Specific CTL Responses in the in vitro Culture (B형 간염 바이러스 X 항원을 면역한 A2Kb Transgenic Mice에서 CD8+ T Cell의 활성화에 의한 X 항원 표현 재조합 Vaccinia Virus에 대한 방어 효과; in vitro 배양을 통한 XEP-3 특이적인 CTL의 반응)

  • Hwang, Yu Kyeong;Kim, Hyung-Il;Kim, Nam Kyung;Park, Jung Min;Cheong, Hong Seok
    • IMMUNE NETWORK
    • /
    • v.2 no.1
    • /
    • pp.41-48
    • /
    • 2002
  • Background: Viral antigens presented on the cell surface in association with MHC class I molecules are recognized by CD8+ T cells. MHC restricted peptides are important in eliciting cellular immune responses. As peptide antigens have a weak immunigenicity, pH-sensitive liposomes were used for peptide delivery to induce effective cytotoxic T lymphocyte (CTL) responses. In the previous study, as the HBx peptides could induce specific CTLs in vitro, we tested whether the HLA-A2/$K^b$ transgenic mice that were immunized by HBx-derived peptides could be protected from a viral challenge. Methods: HBx-peptides encapsulated by pH-sensitive liposomes were prepared. $A2K^b$ transgenic mice were immunized i.m. on days one and seven with the indicated concentrations of liposome-encapsulated peptides. Three weeks later, mice were infected with $1{\times}10^7pfu$/head of recombinant vaccinia virus (rVV)-HBx via i.p. administration. The ovaries were extracted from the mice, and the presence of rVV-HBx in the ovaries was analyzed using human TK-143B cells. IFN-${\gamma}$ secretion by these cells was directly assessed using a peptide-pulsed target cell stimulation assay with either peptide-pulsed antigen presenting cells (APCs), concanavalin A ($2{\mu}g/ml$), or a vehicle. To generate peptide-specific CTLs, splenocytes obtained from the immunized mice were stimulated with $20{\mu}g/ml$ of each peptide and restimulated with peptide-pulsed APC four times. The cytotoxic activity of the CTLs was assessed by standard $^{51}Cr$-release assay and intracellular IFN-${\gamma}$ assay. Results: Immunization of these peptides as a mixture in pH-sensitive liposomes to transgenic mice induced a good protective effect from a viral challenge by inducing the peptide-specific CD8+ T cells. Mice immunized with $50{\mu}g/head$ were much better protected against viral challenge compared to those immunized with $5{\mu}g$/head, whereas the mice immunized with empty liposomes were not protected at all. After in vitro CTL culture by peptide stimulation, however, specific cytotoxicity was much higher in the CTLs from mice immunized with $5{\mu}g/head$ than $50{\mu}g/head$ group. Increase of the number of cells that intracellular IFN-${\gamma}$ secreting cell among CD8+ T cells showed similar result. Conclusion: Mice immunized with XEPs within pH-sensitive liposome were protected against viral challenge. The protective effect depended on the amount of antigen used during immunization. XEP-3-specific CTLs could be induced by peptide stimulation in vitro from splenocytes obtained from immunized mice. The cytotoxic effect of CTLs was measured by $^{51}Cr$-release assay and the percentage of accumulated intracellular IFN-${\gamma}$ secreting cells after in vitro restimulation was measured by flow cytometric analysis. The result of $^{51}Cr$-release cytotoxicity test was well correlated with that of the flow cytometric analysis. Viral protection was effective in immunized group of $50{\mu}g/head$, while in the in vitro restimulation, it showed more spectific response in $5{\mu}g$/head group.

Multicentric T cell lymphoma in a Maltese dog

  • Jung, Ji-Youl;Kang, Sang-Chul;Roh, In-Soon;Sohn, Hyun-Joo;Yun, Young-Min;Kim, Jung-Hun;Lee, Kyoung-Kap;An, Min-Chan;Bae, Jong-Hee;Kim, Jae-Hoon
    • Korean Journal of Veterinary Research
    • /
    • v.47 no.1
    • /
    • pp.85-89
    • /
    • 2007
  • A case of multicentric high grade T cell lymphoma is reported in a 5-year-old male Maltese dog with generalized lymphadenopathy. The dog showed depression, anorexia, blindness, jaundice, arrhythmia, and hematuria for 8 months. Complete blood count and chemistry profile revealed anemia and increased alanine transferase, alkaline phosphatase, total bilirubin, and total cholesterol. Grossly, most of lymph nodes, spleen, and liver were enlarged and neoplastic masses were occupied in these tissues. Histologically, massive accumulation of small noncleaved neoplastic lymphocytes with high mitotic figures was observed in all lymph nodes and spleen. Infiltration of neoplastic lymphocytes was also noted in the lung, liver, kidney, eye, skin, muscle, and bone marrow of femur. Immunohistochemistry revealed that tumor cells were CD3-positive and but CD79a-negative, consistent with T-cell lineage. In our best knowledge, this is the first report of multicentric lymphoma clarified the origin of tumor cells in Korea.

The Screening Condition for the Immune Regulatory Responsor Using Mouse Fetal Thymic Organ Culture (쥐의 태아 흉선 조직 배양을 이용한 면역조절제 검색방법 확립)

  • Lee, Seung-Gak;Song, Min-Dong;Lee, Kwang-Ho
    • Korean Journal of Pharmacognosy
    • /
    • v.28 no.4
    • /
    • pp.286-292
    • /
    • 1997
  • We studied the screening condition for immune regulatory responsor. We focused on the T-lymphocytes leer this purpose. Mouse fetal thymic organ culture (FTOC) system and flow cytometric analysis were mainly used in this experiment. Even if FTOC is carried out in vivo condition, the pattern of thymic development in the condition of FTOC is similar to that of in vivo condition. In this regard, FTOC system might be very powerful tool to screen the immune regulator, especially concerning on T cells. To establish the optimum condition of FTOC to screen the Immune regulator, we focused on the optimum amount of dose and culture period. The cell number and surface antigens on T cells were also analysed by using hemacytometer and flow cytometer. To monitor the differentiation event, anti-CD3, anti-CD4 and anti-CD8 antibodies were used. Alkoxyglycerol and Phellodendri Cortex were used fur positive and negative control, respectively. Astragalus membranceus was used as test sample. From our analysis, we reached to conclusions that the best dose of extract is $50\;{\mu}g/ml$ of culture medium, the best culture period is for 9 days, and ethanol used as solvent has no toxicity to FTOC.

  • PDF

MethA Fibrosarcoma Cells Expressing Membrane-Bound Forms of IL-2 Enhance Antitumor Immunity

  • Sonn, Chung-Hee;Yoon, Hee-Ryung;Seong, In-Ock;Chang, Mi-Ra;Kim, Yong-Chan;Kang, Han-Chul;Suh, Seok-Cheol;Kim, Young-Sang
    • Journal of Microbiology and Biotechnology
    • /
    • v.16 no.12
    • /
    • pp.1919-1927
    • /
    • 2006
  • Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but various unexpected side effects are observed, which may result from the bulk activation of various bystander cells. In this study, we tested tumor vaccines expressing various membrane-bound forms of IL-2 (mbIL-2) on MethA fibrosarcoma cells to focus antitumor immune responses to CTL. Chimeric forms of IL-2 with whole CD4, deletion forms of CD4, and TNF were expressed on the tumor cell surface, respectively. Tumor clones expressing mbIL-2 or secretory form of IL-2 were able to support the cell growth of CTLL-2, an IL-2-dependent T cell line, and the proliferation of spleen cells from 2C TCR transgenic mice that are responsive to the $p2Ca/L^d$ MHC class I complex. Expression of mbIL-2 on tumor cells reduced the tumorigenicity of tumor cells, and the mice that once rejected the live IL-2/TNF tumor clone acquired systemic immunity against wild-type MethA cells. The IL-2/TNF clone was inferior to other clones in tumor formation, and superior in the stimulation of the CD8+ T cell population in vitro. These results suggest that the IL-2/TNF clone is the best tumor vaccine, and may stimulate CD8+ T cells by direct priming. Expression of IL-2/TNF on tumor cells may serve as an effective gene therapy method to ameliorate the side effects encountered in the recombinant cytokine therapy and the conventional cytokine gene therapy using the secretory form of IL-2.

Effects of Orostachys japonicus A. Berger on the Immune System (와송(瓦松) 추출물이 면역체계에 미치는 영향)

  • Kwon, Jin;Han, Kwang-Soo
    • Korean Journal of Medicinal Crop Science
    • /
    • v.12 no.4
    • /
    • pp.315-320
    • /
    • 2004
  • The purpose of this research was to investigate the effect of Orostachys japonicus A. Berger (OJB) on the immune system. Administration of OJB (500 mg/kg) enhanced viability of splenocytes and thymocytes in BALB/c mice, and also OJB increased of splenic T lymphocytes, significantly, increased CD4 positive $T_H$ cells and CD8 positive Tc cells. OJB markedly, enhanced the production of ${\gamma}-interferon$ in mice serum. OJB accelerated the apoptosis of L1210 and U937 leukemia cells and increased the expression of apoptosis-related ICE, c-myc, p53 gene. These results suggest that OJB have an immuno-regulatory and anti-cancer activity.