• 제목/요약/키워드: CD8$^+$ T-cell

검색결과 461건 처리시간 0.033초

Mucosal Immunity Related to FOXP3+ Regulatory T Cells, Th17 Cells and Cytokines in Pediatric Inflammatory Bowel Disease

  • Cho, Jinhee;Kim, Sorina;Yang, Da Hee;Lee, Juyeon;Park, Kyeong Won;Go, Junyong;Hyun, Chang-Lim;Jee, Youngheun;Kang, Ki Soo
    • Journal of Korean Medical Science
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    • 제33권52호
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    • pp.336.1-336.12
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    • 2018
  • Background: We aimed to investigate mucosal immunity related to forkhead box P3 ($FOXP3^+$) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods: Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-$ROR{\gamma}t$ antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin $(IL)-1{\beta}$, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon $(IFN)-{\gamma}$, soluble CD40L, and tumor necrosis factor-${\alpha}$. Results: $FOXP3^+$ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. $ROR{\gamma}t^+$ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 ($9.6{\pm}1.5$ vs. $12.7{\pm}3.0$), IL-21 ($14.9{\pm}1.5$ vs. $26.4{\pm}9.1$), IL-33 ($14.3{\pm}0.9$ vs. $19.1{\pm}5.3$), and $IFN-{\gamma}$ ($15.2{\pm}5.9$ vs. $50.2{\pm}42.4$) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 ($119.1{\pm}79.6$ vs. $52.9{\pm}39.1$) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A ($64.2{\pm}17.2$ vs. $28.3{\pm}10.0$) and IL-22 ($37.5{\pm}8.8$ vs. $27.2{\pm}3.7$) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion: Mucosal immunity analysis showed increased $FOXP3^+$ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.

유육종증 전국실태조사 (National Survey of Sarcoidosis in Korea)

  • 대한결핵 및 호흡기학회 학술위원회
    • Tuberculosis and Respiratory Diseases
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    • 제39권6호
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    • pp.453-473
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    • 1992
  • 연구배경 : 전국 실태조사를 통하여 현재까지 확진된 전국의 유육종증 발생현황을 파악하고 이를 분석하고 외국의 보고와 비교하여 일반 개업의 및 내과 전문개업의 진료활동에 도움이 되도록 하고자 하였다. 방법 : 조사와 분석기간은 1991년 1월부터 1992년 12월까지 2년간으로 정하였으며 자료수집방법은 후향적 방법으로 입원실이 100병상 이상인 213개 종합병원의 내과, 안과, 피부과, 신경내과에 서신을 통한 경험증례를 수집 하였으며 확진예나 의심예가 있었던 경우에 유육종증 증례 기록지를 보내어 정확한 임상 및 검사정보를 수집하여 분석하였다. 결과 : 1) 제 1 차 설문엽서 발송은 입원실이 100병상 이상인 213개 종합병원의 내과, 안과, 피부과, 신경내과의 523개과 과장 및 호흡기 내과를 담당하는 전문의에게 발송하였다. 내과가 213개과로 41%, 피부과가 1087개과로 20%, 안과가 104개과로 20%, 신경과가 100개과로 19%를 차지하였다. 2) 제 1 차 설문조사에 대한 답신은 241개과에서 연락이 있었다(48% 회신율). 3) 확진예 및 의심예는 총 50개과 113예 및 10예가 있다고 보고되었으며 내과가 92예로 81%, 피부과 15예로 13%, 안과, 신경과가 각 3예로 3%를 차지하였다. 자료분석은 총 78예에서 시행되었고 내과 72예로 92%, 피부과 4예로 5%, 신경과 2예로 3%를 차지하였다. 4) 1980년 1에보고 이후 증례가 많은 수로 증가하여 1989년 13예, 19901건 17예, 1991년 18예가 보고되었다. 5) 진단 당시의 연령은 20대, 30대, 40대가 84.4%로 대부분을 차지하고 있었다. 6) 남녀비는 1 : 1.5의 비율로 여자 환자가 많았다. 7) 진단을 받게된 동기로 주소의 빈도로는 호흡기 증상이 48%로 가장 많았고, 피부의 병변, 전신증상, 시각장애, 관절통, 복통, 연하곤란의 순서이었고 무증상이 12예(16%)이었다. 8) 초증상에서 확진을 받을때까지 중앙치는 2개월이었다. 9) 증상의 반도로는 호흡기 증상, 전신증상, 피부증상, 눈 증상, 말초림프구 종창, 신경계증상, 심장증상의 순이었다. 10) 말초혈액검사 소견상 혈색소, 혈구용적치 및 혈소판수는 대부분 정상범위를 나타냈다. 58%의 증례에서 30%미만의 림프구 감소증을 나타냈으며, 임파구 아형으로 T4/T8비는 1.73{\pm}1.16$(0.43~4.62)였다. 43%에서 혈침속도가 상승하였다. 11) 혈청 생화학검사는 대부분 정상범위를 이었다. 혈청 ACE 농도의 평균치는 $66.8{\pm}58.6$(8.8~265) U/L로서 46.2%에서 증가되었다. 42.9%에서 하루 150 mg 이상의 단백뇨 소견을 나타냈고, 36.8%가 하루 300 mg이상의 단백뇨 소견을 나타냈다. 12) 면역학적 검사상 혈청 IgG는 43.5%, IgA는 45.5%, lgM은 59.1%, IgE는 46.7%에서 상승되었고, C3 및 C4는 대부분 정상범위 였으며, ANA는 11%에서 양성을 보였다. Kveim test는 시행된 3예에서 모두 양성을 나타냈다. 13) 폐기능검사중 FVC는 80% 미만인 경우가 17.3%, FEV1은 70% 미만인 경우가 11.5% FEV1/FVC는 70% 미만인 경우가 10%, TLC는 80% 미만인 경우가 15.2%, DLCO는 100% 미만인 경우가 64.7%이었다. 14) 동맥혈가스 분석소견은 PaO2가 90mmHg 미만인 경우가 48.6%, PaCO2는 평균 45mmHg보다 증가된 경우보다 5.7%이었다. 15) 기관지 폐포세척액 검사상 대식세포의 평균 백분율은 $51.4{\pm}19.2%$였고, 임파구의 평균 백분율은 $44.4{\pm}21.1$이였다. 임파구아형은 T4/T8 ratio는 $3.41{\pm}2.07$이였다. 16) 전 검사항목에 대한 남녀 성별간의 유의한 차이는 없었다. 17) 흉부방사선의 분석에서 폐문 임파절 비대를 보인례는 87.9%였고, 78.8%에서는 양측성병변을 9.1%에 일측성 병변을 보였다. 18) Siltzbach의 분류에 의한 병기 구분시 stage 0 : 5%, stage 1 : 58.3%, stage 2 : 28.3%, stage 3 : 8.3%의 분포를 보였다. 19) 흉부 CT를 시행한 54예에서 폐문임파절비대는 50예(92.6%)에서 보였고 이들 중 47예는 양측성 비대였다. 20) 고해상도 CT는 16예에서 시행하였는데, 2예에서는 병변이 없었으며, 폐실질의 병변은 결정성 병변, 소엽간 중격비후, 반점상 국소 폐음영의 순으로 나타났다. 21) 부수적으로 시행한 방사선학적 검사에서 골병변은 1예에서 수근골의 병변을 보였고, 초음파검사에서 2에에서 비장비대의 소견을 보였다. 22) 갈륨스캔은 12에에서 시행하여 폐문 및 종격동 임파절의 흡수증가 소견이 8예에서 보였고, 폐장의 흡수증가는 2예에서 보였다. 23) 조직검사상 가장 많이 시행한 진단방법은 경기관지 폐생검 47.3%이었고, 피부와 종격동 임파절 생검은 각각 34.5%, 말초임파절생검 23.6%, 개흉 폐생검 18.2%, 기관지생검이 16.2%이었다. 2가지 이상의 부위에서 조직검사를 시행한 경우는 52.7%이었다. 한 부위에서만 조직검사를 시행한 26예중 종격동 임파절 생검은 10예, 피부생검 6예, 말초임파절 생검 5예, 개흉폐생검 3예 그리고 경기관지 폐생검 2예이었다. 24) 병리소견상 비건락성 육아종은 100% 모두에서 관찰되었며, 다핵거대 세포는 47.3%, 봉입체는 10.9%, 초자질 섬유화는 34.5%, 괴사 9.1%, reticulin fibrils network 20%, lymphangitic distribution of granuloma 1.8%에서 관찰되었다. 결론 : 유육종 전국 실태조사에 따른 영상소견, 검사실소견, 방사선소견, 병리소견을 분석해 본 결과, 우리나라 유육종 환자들도 다소 차이는 있었지만 외국의 보고들과 유사한 소견들을 나타냈으며, 향후로는 이들에 대한 결과들을 추가분석하여, 유육종 진단에 도움을 줄 수 있고, 임상적 지표로 이용될 수 있는 검사항목을 찾아내는 것이 과제라 할 수 있겠다. 유육종증에 대한 자료는 대한 결핵 맺 호흡기학회에 보관이 되어 있음을 알려드립니다.

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Effect of Zedoariae rhizoma on Bronchial Inflammation and Allergic Asthma in Mice

  • Ahn, Jong-Chan;Ban, Chang-Gyu;Park, Won-Hwan
    • 동의생리병리학회지
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    • 제20권6호
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    • pp.1636-1648
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    • 2006
  • There are detailed descriptions of the clinical experiences and prescriptions of asthma in traditional Korean medicine. Zedoariae rhizoma is one of the Korean herbal medicines used to treat bronchial asthma and allergic rhinitis for centuries. However, the therapeutic mechanisms of this medication are still far from clear, In this study, a house-dust-mite (Dermatophagoides pteronyssinus [Der p])-sensitized murine model of asthma was used to evaluate the immunomodulatory effect of Zedoariae rhizoma on the allergen-induced airway inflammation in asthma. Three different protocols were designed to evaluate the treatment and/or long-term prophylacitic effect of Zedoariae rhizoma in Der p-sensitized mice. Cellular infiltration and T-cell subsets in the bronchoalveolar lavage fluid (BALF)of allergen-challenged mice were analyzed. Intrapulmonary lymphocytes were also isolated to evaluate their response to allergen stimulation. When Zedoariae rhizoma was administered to the sensitized mice before AC (groups A and C), it suppressed airway inflammation by decreasing the number of total cells and eosinophil infiltration in the BALF, and downregulated the allergen- or mitogen-induced intrapulmonary lymphocyte response of sensitized mice as compared to those of controls. This immunomodulatory effect of Zedoariae rhizoma may be exerted through the regulation of T-cell subsets by elevation or activation of the CD8+ and double-negative T-cell population in the lung. However, the administration of Zedoariae rhizoma to sensitized mice 24 h after AC (group B) did not have the same inhibitory effect on the airway inflammation as Zedoariae rhizoma given before AC. Thus, the administration of Zedoariae rhizoma before AC has the immunomodulatory effect of reducing bronchial inflammation in the allergen-sensitized mice. On the other hand, to determine the potentiality of prophylactic and/or therapeutic approaches using a traditional herbal medicine, Zedoariae rhizoma, for the control of allergic disease, we examined the effects of oral administration of Zedoariae rhizoma on a murine model of asthma allergic responses. When oral administration of Zedoariae rhizoma was begun at the induction phase immediately after OVA sensitization, eosinophilia and Th2-type cytokine production in the airway were reduced in OVA-sensitized mice following OVA inhalation. These results suggest that the oral administration of Zedoariae rhizoma dichotomously modulates allergic inflammation in murine model for asthma, thus offering a different approach for the treatment of allergic disorders.

MTHFR 3'-untranslated region polymorphisms contribute to recurrent pregnancy loss risk and alterations in peripheral natural killer cell proportions

  • Kim, Eun Sun;Kim, Jung Oh;An, Hui Jeong;Sakong, Jung Hyun;Lee, Hyun Ah;Kim, Ji Hyang;Ahn, Eun Hee;Kim, Young Ran;Lee, Woo Sik;Kim, Nam Keun
    • Clinical and Experimental Reproductive Medicine
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    • 제44권3호
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    • pp.152-158
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    • 2017
  • Objective: To identify the associations between polymorphisms of the 3'-untranslated region (UTR) of methylenetetrahydrofolate reductase (MTHFR) gene, which codes for an important regulatory enzyme primarily involved in folate metabolism, and idiopathic recurrent pregnancy loss (RPL) in Korean women. Methods: The study population comprised 369 RPL patients and 228 controls. MTHFR 2572C > A, 4869C > G, 5488C > T, and 6685T > C 3'-UTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis or by TaqMan allelic discrimination assays. Natural killer cell proportions were determined by flow cytometry. Results: The MTHFR 2572-5488-6685 (A-C-T) haplotype had an adjusted odds ratio of 0.420 (95% confidence interval, 0.178-0.994; p= 0.048) for RPL. Analysis of variance revealed that MTHFR 4869C > G was associated with altered $CD56^+$ natural killer cell percentages (CC, $17.91%{\pm}8.04%$; CG, $12.67%{\pm}4.64%$; p= 0.024) and folate levels (CC, $12.01{\pm}7.18mg/mL$; CG, $22.15{\pm}26.25mg/mL$; p= 0.006). Conclusion: Variants in the 3'-UTR of MTHFR are potential biomarkers for RPL. However, these results should be validated in additional studies of ethnically diverse groups of patients.

홍역 후 천명환아의 기도내 세포양상 및 IL-8치 (Bronchoalveolar Cellularity and IL-8 Levels in Patients with Post-measles Wheezing)

  • 정다은;김병의;정주영;김정연;마상혁;김창근
    • Clinical and Experimental Pediatrics
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    • 제46권8호
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    • pp.763-768
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    • 2003
  • 목 적 : 본 연구의 목적은 홍역 바이러스 감염 후 발생한 천명성 질환에서 기도내 세포양상과 화학주성인자IL-8의 변화를 알아봄으로써 홍역 후 후기 폐 합병증의 병태생리를 밝히는데 도움을 얻고자 했다. 방 법 : 이전에 건강했으나, 홍역 폐렴 후 적어도 3회 이상의 천명으로 내원하여 고식적인 천명치료를 하였으나 이에 잘 반응하지 않아 기관지내시경을 시행받은 12명의 환아(홍역 후 천명군, 중간연령 1.3세)를 후향적으로 분석하였다. 이들은 홍역 감염 평균 6개월(1-15개월) 후 고해상 전산화 단층촬영(HRCT)을 시행 받았다. 기관지폐포세척액에서는 총세포수와 세포분획을 분석하였다. IL-8 농도는 ELISA로 측정하였다. 이 결과들을 7명의 정상 대조아(대조군, 중간연령 7.4세)와 비교하였다. 결 과 : 1) 기관지폐포세척세포의 비교에서 호중구 분획이 홍역 후 천명군에서 16.0%로 대조군의 3.8% 비해 의미있게 증가되어 있었다(P<0.01). 그 외 임파구나 호산구의 분획은 양군간의 차이가 없었다. T세포아형에 대한 면역조직화학염색 결과에서는 CD4+/CD8+비가 1/14.1로 CD8+이 현저하게 상승되어 있었다. 2) IL-8치의 비교에서는, 홍역 후 천명군($mean{\pm}SD$, $512.7{\pm}324.0pg/mL$)에서 대조군($41.7{\pm}67.7pg/mL$)에서 보다 의미있게 높았다(P<0.01). 3) BAL 호중구와 IL-8치의 상관성에 관한 분석에서 홍역 후 천명군의 BAL 호중구와 IL-8치는 서로 유의한 상관관계를 나타내었다(r=0.816, P=0.001). 4) 의미있는 HRCT 소견으로는 모자이크성 관류, 기관지 확장, 기관지벽 비후 그리고 폐혈관 감소로 후기 만성 폐합병증 소견을 보여 주었다. 결 론 : 홍역 후 천명성 질환에서 기도내 호중구와 IL-8치가 현저히 상승하였으며 호중구와 IL-8은 유의한 상관관계를 나타내었다 따라서 홍역 후 천명의 병태생리에 기도내 호중구와 IL-8의 역할이 중요하리라 생각된다.

정보소양과 경제윤리의 실태와 경제교육 과제 (A Survey Research on the Economic Ethics and Information Literacy)

  • 조병철;남상섭
    • 정보학연구
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    • 제8권3호
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    • pp.117-129
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    • 2005
  • The topic of this study is a survey research about the economic recognition related to economic ethics and information literacy of students(6,779) extend from elementary school to university. First, for the ability to use computers, it is recognizing that 49.6% of students are normal, 38.6% are superior, and 12.8% are inferior. In part of class, it tends to recognize that it is the superior as the level of school is the lower excepting middle school students. Second, we can find great difference between male students and female students related to purpose of using internet, 79.8% of male students are using computer to play game or entertainment(1), search data or knowledge(2), chatting or massenger(3), 70.1% of female students are using internet to search data or knowledge(1), chatting or massenger(2) and meeting of similar taste. Third, it shows a tendency that the economic activity using internet or cell-phone increases faster as the level of schools is higher. In detail, they primarily use buying or settlement of products(63%), purchasing internet service(20.9%). Fourth, for using illegal CD, not only they didn't feel guilty in all levels of schools, excepting university students, it is showed that the trust of intellectual poverty right is weaker as the level of schools is higher. So, it is becoming serious problems. It seems a task which should be supplemented through economic education of schools in the future.

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DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice

  • Hong Min Kim;Mi-Hye Kwon;Eun Soo Lee;Kyung Bong Ha;Choon Hee Chung
    • Journal of Yeungnam Medical Science
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    • 제41권2호
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    • pp.103-112
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    • 2024
  • Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods: Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW 264.7 cells. Results: DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8+ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

정신분열증 환자에서 Interleukin-$1{\beta}$, -2, -6 생산능과 혈청농도 변화에 관한 연구 (Study on Alteration of Interleukin-$1{\beta}$, -2, -6 Production and Serum Level in Schizophrenic Patients)

  • 김용구;이민수;서광윤
    • 생물정신의학
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    • 제1권1호
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    • pp.98-108
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    • 1994
  • The etiology and pathophysiology of schizophrenia remain unknown. It has been postulated that infectious-autoimmune process may play a role in the pathogenesis of symptoms in some schizophrenic patients. Findings of altered interleukin(IL) regulation have been regarded as additional proof that schzophrenia has an infectious-autoimmune background. In the present study, we measured mitogen-stimulated production of and serum level of IL-$1{\beta}$, IL-2, IL-6 using ELISA in 16 neuroleptic-free schizophrenic patients and in 16 age, sex matched healthy controls. The results were as follows : 1) There was a significant decrease of IL-2 production in schizophrenic patients than in normal controls(respectively $1.90{\pm}0.13ng/m{\ell}$, $2.79{\pm}0.14ng/m{\ell}$, p<0.001). But there was no significant difference of IL-$1{\beta}$ production and IL-6 production between schizophrenic patients and normal controls. 2) There was a significant increase of serum level of IL-2 in schizophrenic pateitns than in normal controls(respectively $184.8{\pm}12.8pg/m{\ell}$, $104.2{\pm}34.2pg/m{\ell}$, p<0.01). Serum level of IL-$1{\beta}$ was partially detected in both groups and serum level of IL-6 was not detected in both groups. 3) There was no significant differences of IL-$1{\beta}$, -2, -6 production & serum level of IL-2 according to male vs female, paranoid type vs undifferentiated type, drug-naive group vs drug-free group in schizophrenic patients. 4) There was significant correlation between IL-$1{\beta}$ and IL-6 production(r=0.86, p<0.001). No correlation between IL-$1{\beta}$, -2, -6 production, serum level of IL-2 and age, duration of illness, and BPRS score was found. It has been suggested that the low lymphocyte production of IL-2 in the patients with autoimmune disease occurs because the T cells are activated and lymphocyte-derived IL-2 has been released into the serum. The authors suggest that decreased IL-2 production in our schizophrenic patients is due to increased IL-2 serum level in those patients. Thus our finding of low IL-2 production and high serum level of IL-2 in our schizophrenic patients is compatible with the possibility that our patients have an autoimmune process. Further study on relationship between IL alteration and other immunological abnormalities(the presence of serum autoantibody and of anti-brain antibody, $CD4^+$, $CD8^+$ cell index, etc) in schizophrenic patients will be warranted.

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Multiple Cytotoxic Factors Involved in IL-21 Enhanced Antitumor Function of CIK Cells Signaled through STAT-3 and STAT5b Pathways

  • Rajbhandary, S.;Zhao, Ming-Feng;Zhao, Nan;Lu, Wen-Yi;Zhu, Hai-Bo;Xiao, Xia;Deng, Qi;Li, Yu-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권10호
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    • pp.5825-5831
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    • 2013
  • Background/Objectives: Maintenance of cellular function in culture is vital for transfer and development following adoptive immunotherapy. Dual properties of IL-21 in activating T cells and reducing activation induced cell death led us to explore the mechanism of action of IL-21 enhanced proliferation and cytotoxic potential of CIK cells. Method: CIK cells cultured from PBMCs of healthy subjects were stimulated with IL-21 and cellular viability and cytotoxicity to K562 cells were measured. To elucidate the mechanism of action of IL-21, mRNA expression of cytotoxic factors was assessed by RT-PCR and protein expression of significantly important cytotoxic factors and cytokine secretion were determined through flow cytometry and ELISA. Western blotting was performed to check the involvement of the JAK/STAT pathway following stimulation. Results: We found that IL-21 did not enhance in vitro proliferation of CIK cells, but did increase the number of cells expressing the CD3+/CD56+ phenotype. Cytotoxic potential was increased with corresponding increase in perforin ($0.9831{\pm}0.1265$ to $0.7592{\pm}0.1457$), granzyme B ($0.4084{\pm}0.1589$ to $0.7319{\pm}0.1639$) and FasL ($0.4015{\pm}0.2842$ to $0.7381{\pm}0.2568$). Interferon gamma and TNF-alpha were noted to increase ($25.8{\pm}6.1ng/L$ to $56.0{\pm}2.3ng/L$; and $5.64{\pm}0.61{\mu}g/L$ to $15.14{\pm}0.93{\mu}g/L$, respectively) while no significant differences were observed in the expression of granzyme A, TNF-alpha and NKG2D, and NKG2D. We further affirmed that IL-21 signals through the STAT-3 and STAT-5b signaling pathway in the CIK cell pool. Conclusion: IL-21 enhances cytotoxic potential of CIK cells through increasing expression of perforin, granzyme B, IFN-gamma and TNF-alpha. The effect is brought about by the activation of STAT-3 and STAT-5b proteins.

Reconstructed Adeno-Associated Virus with the Extracellular Domain of Murine PD-1 Induces Antitumor Immunity

  • Elhag, Osama A.O.;Hu, Xiao-Jing;Wen-Ying, Zhang;Li, Xiong;Yuan, Yong-Ze;Deng, Ling-Feng;Liu, De-Li;Liu, Ying-Le;Hui, Geng
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.4031-4036
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    • 2012
  • Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.