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제 1형 당뇨병 환자에서의 자연살해세포 활성능, 항체의존성 세포독성능 및 Interleukin-2의 생성에 관한 연구

Issue Date
1988
Description
의학과/석사
Abstract
[한글] 제 1형 당뇨병의 병인으로는 유전적 소인과 환경적 요인과 더불어 체액성 면역과 세포성 면역기전의 이상이 췌도세포 소실에 직접 관련되어 있는 것으로 알려져 있다. 특히 세포성 면역에 관여하는 자연살해세포 활성능(Natural Killer cell activity), 항체의존성 세포독성능(Antibody dependent cell mediated cytotoxicity) 및 최근에 연구되고 있는 interleukin-2의 이상이 병인으로 지적되고 있지만, 국내에서는 이에대한 연구가 드문 실정이다. 이에 저자는 제 1형 당뇨병 환자 13예와 정상대조군 29예를 대상으로, K562 세포 및 L1210 세포를 표적세포로 자연살해세포 활성능과 항체의존성 세포독성능을 측정하고, CTLL2 세포주를 이용한 interleukin-2 생성을 연구하여 다음과 같은 결과를 얻었다. 제 1형 당뇨병환자에서, 자연살해세포 활성능은 정상대조군에 비해 의의있게 감소되어 있었으며(46.2±15.8 vs 31.0±14.5%, p<0.01), 항체의존성 세포독성능 역시 제 1형 당뇨병 환자에서 정상대조군 보다 유의하게 낮았다(40.6±19.9 vs 57.7±10.8%, p<0.02). 또한 항체의존성 세포독성능과 질병의 이환기간과는 역 상관관계(r=-0.575)를 보였다. Interleukin-2의 생성은 제 1형 당뇨병 환자에서 정상대조군에 비해 현저히 감소되어 있는 소견을 보였으나(8.1±2.0 vs 1.4±1.9 Unit, p<0.001), interleukin-2의 측정값과 자연살해세포 활성능 또한 항체의존성 세포 독성능과의 사이에서 유의할 만한 상관관계를 찾아볼 수 없었다(r=0.106 및 r=0.08). 이상의 결과로 제 1형 당뇨병 환자에서는 자연살해세포 활성능 및 항체의존성 세포독성능이 저하되어 있었고, cytokine의 일종인 interleukin-2의 생성이 감소되어 있는 것으로 보아, 이러한 세포면역기전의 변화가 유전적소인과 더불어 바이러스등의 환경적 요인에 대한 감수성을 높임으로써 당뇨병의 병인에 중요한 역할을 할 것으로 생각된다 Natural Killer Cell Activity, Antibody Dependent Cell Mediated Cytotoxsicity and Synthesis of Interleukin-2 in Type I Diabetics Sung-Chul Hwang Department of Medical Science, The Graduate School Yonsri University (Direcred by Prof. Kap Bum Huh, M.D.) There is a growing body of evidence that immunologic abnormalities as well as genetic and environmental factors are involved in the pathogenesis of type Ⅰ diabetes. Recent reports indicate the importance of cell mediated immunities and alterations in various immune regulators such as natural killer cell activity(NK activity), antibody dependent cell mediated cytotoxicity(ADCC) and te production of interleukin-2. In this study, natural killer cell activity and antibody dependent cell mediated cytotoxicity were measured using **5] Cr labeled K562 and L1210 cell lines and the synthesis of interleukin-2 was assayed using interleukin-2 dependent CTLL2 cell line in 13 type Ⅰ diabetics and 29 controls. The mean natural killer cell activity was decreased in type Ⅰ diabetics as compared with controls(p<0.01).significant depression in antibody dependent cell mediated cytotoxicity was observed in type Ⅰ diabetics than in controls(p<0.02). In addition, there seemed to be an inverse correiation between the level of ADCC and the duration of the diabetes(r=-0.575). Interleukin-2 production was markedly impaired in type Ⅰ diabetic as compared with controls(p<0.001) but no correlation was noted between interleukin-2 production with either NK cell activity or ADCC. Moreover, these immunologic parameters did not seemed to be influenced by factors such as prior insulin treatment or he degree of glycemic control as represented by fasting blood sugar and glycosylated hemoglobin. In conclusion, there seemed to exist an impairment of NK cell activity and antibody dependent cell mediated cytotoxicity associated with a deficient production of interleukin-2 in type Ⅰ diabetics which, in conjunction with genetic and environmental factors, might play an important role in the immune destruction of islet cells and triggering of autoimmunity.
[영문] There is a growing body of evidence that immunologic abnormalities as well as genetic and environmental factors are involved in the pathogenesis of type Ⅰ diabetes. Recent reports indicate the importance of cell mediated immunities and alterations in various immune regulators such as natural killer cell activity(NK activity), antibody dependent cell mediated cytotoxicity(ADCC) and te production of interleukin-2. In this study, natural killer cell activity and antibody dependent cell mediated cytotoxicity were measured using **5] Cr labeled K562 and L1210 cell lines and the synthesis of interleukin-2 was assayed using interleukin-2 dependent CTLL2 cell line in 13 type Ⅰ diabetics and 29 controls. The mean natural killer cell activity was decreased in type Ⅰ diabetics as compared with controls(p<0.01).significant depression in antibody dependent cell mediated cytotoxicity was observed in type Ⅰ diabetics than in controls(p<0.02). In addition, there seemed to be an inverse correiation between the level of ADCC and the duration of the diabetes(r=-0.575). Interleukin-2 production was markedly impaired in type Ⅰ diabetic as compared with controls(p<0.001) but no correlation was noted between interleukin-2 production with either NK cell activity or ADCC. Moreover, these immunologic parameters did not seemed to be influenced by factors such as prior insulin treatment or he degree of glycemic control as represented by fasting blood sugar and glycosylated hemoglobin. In conclusion, there seemed to exist an impairment of NK cell activity and antibody dependent cell mediated cytotoxicity associated with a deficient production of interleukin-2 in type Ⅰ diabetics which, in conjunction with genetic and environmental factors, might play an important role in the immune destruction of islet cells and triggering of autoimmunity.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/117434
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2. 학위논문 > 1. College of Medicine (의과대학) > 석사
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