화상환자에서 면역억제 기전

정태호,황일우,장수일,김문규,서정민,정치영,김정철 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.4

목적 : 본 연구는 화상환자에서 면역이상의 기전을 조사코져 T-세포의 활성을 나타내는 가용성 interleukin-2 수용체(IL-2R), 대식세포의 활성을 나타내는 neopterin, tumor necrosis factor(TNF) 및 interleukin-6 (IL-6), 그리고 호중구의 활성을 반영하는 elastase-α1-antitrypsin을 측정하였다. 또한 lipopolysaccharide(LPS)가 이들 면역세포의 활성화에 미치는 영향을 조사하였다. 대상 및 방법 : 30예의 화상환자를 대상으로 화상후 1일, 7일, 14일, 21일, 28일에 각각 혈액을 채취하여 혈청중 가용성 IL-2R, TNF, IL-6, 그리고 elastase-α1-antitrypsin은 각각 효소면역법으로, 혈청중 neopterin은 radioimmunoassay법으로 측정하였다. LPS가 말초 단핵세포에 미치는 영향은 역전사 중합효소 연쇄반응을 통하여 각종 cytokines의 mRNA 발현을 측정하였다. 결과 : 화상환자에서 혈청중 가용성 IL-2R은 화상후 1일째부터 대조군에 비하여 유의성 있게 증가되어 7일과 14일째에 최고치를 나타냈으며 그 이후에는 다소 감소하였으나 대조군보다는 유의한 증가를 나타냈다. 화상환자를 중화상, 중등도화상, 경도화상으로 분류하여 혈청중 가용성 IL-2R 치를 비교해본 결과 중증 화상일수록 더욱 높은 치를 나타냈다. 화상환자에서 혈청중 neopterin 역시 화상후 1일째부터 증가되어 전 관찰기간 동안 대조군에 비해 유의한 높은 치를 나타냈다. 경도화상과 중등도 화상에서는 서로 유의한 차이를 보이지 않았으나 중환자에서는 경도 혹은 중등도 화상환자에 비해 유의한 증가를 보였다. 화상환자에서 혈청중 TNF 농도는 화상후 1일부터 증가되어 관찰전기간에 걸쳐 유의한 증가를 나타냈으며 중등도 화상환자에서 가장 높은 치를 보였다. 혈청중 IL-6치 역시 화상 전기간에 걸쳐 대조군보다 유의한 증가를 나타냈으며 중화상 환자에서 가장 높은 치를 나타냈다. 화상은 또한 혈청중 elastase-α1-antitrypsin 농도를 현저히 증가시켰다. 즉 화상후 1일에 elastase-α1-antitrypsin 농도는 정상인보다 5배 높았으며 그 이후 약 4주간 계속 높은 농도를 유지하다가 환자가 회복되면서 감소하는 경향을 나타내었다. 중등도화상 및 중화상환자의 혈청중 elastase-α1-antitrypsin 농도는 경도 화상환자에서 비해 유의한 증가를 보였다. 한편 화상환자에서 면역이상을 초래하는 주된 요인으로 여겨지는 lipopolysaccharide는 면역세포를 총체적으로 활성화시켜 IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, IFN-γ, TGF-β, GM-CSF, IL-2R의 유전자발현을 현저히 증가시켰다. 결론 : 화상환자에서 T-세포, 대식세포, 호중구의 활성화를 반영하는 가용성 IL-2R, neopterin, ,TNF, IL-6, elastase-α1-antitrypsin치가 혈중에 증가되어 있으며 화상의 정도가 심할수록 더 높았다. Cell-mediated immunity frequently becomes severely impaired after thermal injury. However, the cause of postburn immune dysfunction is unclear and controversy exists over both pathophysiology and clinical relevance of these abnormalities. This study was undertaken to investigate the immune responses in vivo of patients with burn. Levels of soluble IL-2R, a sensitive marker of T-cell activation, levels of serum TNF, IL-6, and neopterin, an index of macrophage activation, and levels of serum elastase-α1-antitrypsin, an index of neutrophil activation, were measured in serial serum samples taken from 30 burned patients. In patients with burn, soluble IL-2R levels were increased over a 4-week interval with peak concentrations reached during the 2nd week after burn. Patients with severe burn showed a higher soluble IL-2R levels than those with mild or moderate burn. In addition soluble IL-2R significantly correlated with burn size. The levels of serum neopterin were already increased at the first day following burn, and remained at a high level throughout the total period studied (28 days). Patients with severe burn showed significantly higher concentration of serum neopterin than mild or moderate burn. There was positive relationship between the burn sizes and the levels of neopterin. A significant positive correlation was also found between serum soluble IL-2R levels and neopterin levels in burn patients. Levels of serum TNF and IL-6 were also significantly increased over a 4-week interval in burn patients. The levels of serum elastase-α1-antitrypsin were also already increased at the first day following burn, and remained at a high level over a 4-week. Patients with moderate or severe burn showed significantly higher concentration of serum elastase-α1-antitrypsin than those with mild burn. There was no significant relationship between the burn extent and the level of elastase-α1-antitrypsin. LPS increased the transcription of all the cytokines we examined in peripheral mononuclear cells, i.e., IL-1α, IL-1β, IL-2, IL-4, IL-5_IL-6, IL-8, IL-10, TNF, TGF-β, GM-CSF, and IL-2R. We conclude that soluble IL-2R, neopterin, TNF, IL-6, and elastase-α1-antitrypsin might be useful parameters for monitoring of the clinical course in burn patients. Moreover, they indicate that T-cell, macrophage, and neutrophil activation might play the central role in the pathogenesis of the immuno-logic and metabolic disturbance that follows thermal injury.

주조직적합항원이 불일치하는 마우스 동종 조혈모세포이식에서 IL-2로 유도된 CD4+CD25+ T세포를 이용한 이식편대숙주병의 억제

현재호,정대철,정낙균,박수정,민우성,김태규,최병옥,김원일,한치화,김학기,Hyun, Jae Ho,Jeong, Dae Chul,Chung, Nak Gyun,Park, Soo Jeong,Min, Woo Sung,Kim, Tai Gyu,Choi, Byung Ock,Kim, Won Il,Han, Chi Wha,Kim, Hack Ki 대한면역학회 2003 Immune Network Vol.3 No.4

Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

Interferon-γ Inhibits in vitro Mobilization of Eosinophils by Interleukin-5

Park, Choon-Sik,Choi, Eun Nam,Kim, Jung Sun,Choi, Yun Sung,Rhim, Tai Youn,Chang, Hun Soo,Chung, Il Yup S. Karger AG 2005 International archives of allergy and immunology Vol.136 No.3

<P><I>Background:</I> Th2 cytokines play pivotal roles in allergic inflammation, including eosinophilia, and their actions are antagonized by Th1 cytokines, conferring them therapeutic potential. <I>Methods:</I> In this study, we examined the ability of a number of cytokines to suppress the activation of eosinophils that function as effector cells for allergic airway diseases. <I>Results:</I> Interleukin (IL)-5, IL-6, and tumor necrosis factor (TNF) induced an eosinophil shape change, whereas interferon (IFN)-γ significantly inhibited the shape change. Other cytokines, including IL-1β, IL-4, IL-10 and IL-13, had little or only slightly enhancing or reducing effects on the shape change. We further analyzed the IFN-γ effect, showing that pretreatment with IFN-γ strongly suppressed IL-5-induced eosinophil shape change, and cycloheximide (CHX) abrogated the suppression by IFN-γ, suggesting that new protein synthesis is required for the inhibitory effect by this cytokine. In agreement with these results, IFN-γ blocked the eosinophil migration and ERK phophorylation induced by IL-5, and the addition of CHX restored eosinophil chemotaxis. <I>Conclusions:</I> Collectively, IFN-γ may attenuate eosinophilic inflammation by directly negating eosinophil mobilization.</P><P>Copyright © 2005 S. Karger AG, Basel</P>

Effect of Feed Selenium-lysine Supplementation on Milk Compositions and Serum Biochemical Indices in Saanen Dairy Goats

Tae-Il Kim,Dong-Hyun Lim,Tai-Young Hur,Seung-Min Ha,Hyun-Jong Kim,Seong-Min Park,Ji-Hoo Park,Sang-Bum Kim,Ji-Hwan Lee,Hyun-Joo Lim,Jeong-Sung Jung,Ha-Yeon Jeong,Jay Lee,Kwang-Seok Ki,Vijayakumar Mayak 경상대학교 농업생명과학연구원 2019 농업생명과학연구 Vol.53 No.4

An experiment was carried out to assess the effect of feed selenium-lysine (Se-Lys) supplementation on milk compositions and serum biochemical indices in Saanen dairy goats in Korea. A total of twelve 36 months old Saanen lactating dairy goats (47±6.21 kg) fed the similar dry matter intake twice a day at 2% of BW (DMI) (10.9% moisture of concentrate and 19% moisture of roughage), milk yield (2.5 kg/d) and parity (2) were randomly selected and subjected for the present study, divided into two groups with six goats in each group. The goats in the control group received rice hulls (10 g/ day) only, and did not receive Se-Lys; goats in the treatment group were fed 0.06 g of Se-Lys with 10 g of rice hulls every day before feeding roughage for six weeks. The milk sample was collected every week, and its compositions were analyzed. The results of the present study showed that there is no significantly increased milk production in Se-Lys treated group goats when compared with control group goats. But, Se-Lys treatment significantly increased the milk protein content (3.98±0.16%), fat (3.72±0.27%), lactose (4.07±0.14%), total solids (12.51±0.28%) and urea (14.42±1.45 mg/dl) content as compared to the control group goats (p<0.05). The somatic cell counts (207,740±28.81 cells/ml) were significantly lower in the Se-Lys treated group than in the control group (p<0.05). Also, the results of the current study showed that supplementation of Se-Lys were significantly decreased the blood biochemical indices of IL-6 (34.34±6.04 pg/ml), TNT-α (0.56±0.22 ng/ml), MDA (5.07±1.03 ng/ml), GPx-1 (9.07±5.17 ng/ml), sCD4 (2.64±1.02 ng/ml) and sCD8 (5.08±2.08 ng/ml) level when compared with without addition of Se-Lys group dairy goats (p<0.05). On the other hand, the selenoprotein P (1,580.18±127.62 ng/ml) level was significantly higher in Se-Lys supplemented group than in the control group (p<0.05). Based on the study results, it was concluded that feed Se-Lys supplementation may improve milk yield with positively improved protein, fat, lactose, total solids, urea content, and biochemical indices without negative effects on milk production traits.

An optimized peptide vaccine strategy capable of inducing multivalent CD8 ⁺ T cell responses with potent antitumor effects

Cho, Hyun-Il,Jung, Soo-Hyun,Sohn, Hyun-Jung,Celis, Esteban,Kim, Tai-Gyu TaylorFrancis 2015 Oncoimmunology Vol.4 No.11

<P>Therapeutic cancer vaccines are an attractive alternative to conventional therapies for treating malignant tumors, and successful tumor eradication depends primarily on obtaining high numbers of long-lasting tumor-reactive CD8<SUP>+</SUP> T cells. Dendritic cell (DC)-based vaccines constitute a promising approach for treating cancer, but in most instances low immune responses and suboptimal therapeutic effects are achieved indicating that further optimization is required. We describe here a novel vaccination strategy with peptide-loaded DCs followed by a mixture of synthetic peptides, polyinosine-polycytidylic acid (poly-IC) and anti-CD40 antibodies (TriVax) for improving the immunogenicity and therapeutic efficacy of DC-based vaccines in a melanoma mouse model. TriVax immunization 7–12 d after priming with antigen-loaded DCs generated large numbers of long-lasting multiple antigen-specific CD8<SUP>+</SUP> T cells capable of recognizing tumor cells. These responses were far superior to those generated by homologous immunizations with either TriVax or DCs. CD8<SUP>+</SUP> T cells but not CD4<SUP>+</SUP> T cells or NK cells mediated the therapeutic efficacy of this heterologous prime-boost strategy. Moreover, combinations of this vaccination regimen with programmed cell death-1 (PD-1) blockade or IL2 anti-IL2 antibody complexes led to complete disease eradication and survival enhancement in melanoma-bearing mice. The overall results suggest that similar strategies would be applicable for the design of effective therapeutic vaccination for treating viral diseases and various cancers, which may circumvent current limitations of cell-based cancer vaccines.</P>

굴피나무잎 활성성분의 약리작용

김양일,조성익,조태순 성균관대학교 약학연구소 1997 成均藥硏論文集 Vol.9 No.1

In an effort to screen new antitumor agents from various extraction-fractions of 60 plants cytotoxicity-oriented screening was performed. Based on the high cytotoxicity against the human cell lines Platycarya strobilacea was selected and 9 main components were isolated from its leaves for further investigation of in vitro cytotoxicity and in vivo antitumor activity as well as their other putative biological activities such as antiinflammatory, antiallergic, and whitening effects. Seven human tumor cell lines were employed for the observation of in vitro cytotoxicity and P388-leukemia were used for the evalution of in vivo antitumor effects. Compound 1 showed the highest cytotoxicity against all human tumor cell lines tested. In experiment of in vivo antitumor activity, compound 1 increased the life-span of CDF1 mice treated with an ascitic form of P388 leukemia. In experiments to observe antiinflammatory and antiallergic activity, compound 1 reduced the IL-3-and IL-5-dependent Y16 cell growth, while they did not change cyclooxygenase activity of prostaglandin H_2 synthase. Compound 1 and 2 strongly inhibited the specific binding of PAF to its receptors in rabbit platelet rich plasma. Compound 3, 6, 8, and 9 showed tyrosinase activity. Taken together the results demonstrated that compound 1 has the potent cytotoxicity against the various cancer cell lines, while other compounds exhibit the moderate antitumor, antiinflammatory, antiallergic, and whitening effects.

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)의 첨가가 생쥐 수정란의 발생과 착상관련 유전자 발현에 미치는 영향

김동훈,고덕성,이회창,이호준,강희규,김태전,박원일,김세웅,Kim, Dong-Hoon,Ko, Duck-Sung,Lee, Hoi-Chang,Lee, Ho-Joon,Kang, Hee-Gyoo,Kim, Tai-Jeon,Park, Won-Il,Kim, Seung-Samuel 대한생식의학회 2002 Clinical and Experimental Reproductive Medicine Vol.29 No.2

Objective : The purpose of the current series of experiments were to assess the effect of GM-CSF, as a medium supplement, on the development of mouse embryos and the expression of LIF and IL-1? mRNA. Materials and Methods: Mouse 2-cell embryos were collected from the oviducts of 6 weeks old ICR mice at 48 hours after hCG injection. Embryos were cultured in P-1 medium supplemented with mouse GM-CSF (0, 1, 5, 10 ng/ml). The embryo development to blastocysts and hatching blastocysts was assessed and the cell number in blastocyst was also examined. Using RT-PCR, the expressions of LIF and IL-1? mRNA in blastocyst were evaluated in the GM-CSF supplemented group and control group. Results: In mouse, the addition of GM-CSF increased the percentage of blastocysts (65.5%, 68.6%, 73.0% and 76.1% for control and 1, 5 and 10 ng/ml, respectively), and increased the proportion of hatching blastocysts (35.2%, 36.4%, 43.2% and 53.0% for control and 1, 5 and 10 ng/ml, respectively). The mean cell numbers in blastocyst were significantly increased in GM-CSF supplemented groups compared to control group. LIF and IL-1? expression in blastocyst were significantly higher in GM-CSF supplemented group than in control group. Conclusion: The results of experiment by mouse embryos showed beneficial effects of GM-CSF as a medium supplement. Furthermore, the addition of GM-CSF significantly increased the expression of LIF and IL-1? in mouse embryos. These results suggest that GM-CSF might be a important molecule in embryo implantation.

Triple costimulation via CD80, 4-1BB, and CD83 ligand elicits the long-term growth of Vγ9Vδ2 T cells in low levels of IL-2

Cho, Hyun-Woo,Kim, Su-Yeon,Sohn, Dae-Hee,Lee, Min-Ji,Park, Mi-Young,Sohn, Hyun-Jung,Cho, Hyun-Il,Kim, Tai-Gyu Federation of American Societies for Experimental 2016 Journal of Leukocyte Biology Vol.99 No.4

<P>Human gamma delta T cells play important roles in the regulation of infection and cancer. To understand the roles of costimulatory signals in activation and expansion ex vivo, V gamma 9V delta 2 T cells were grown with artificial APCs that express CD83, 4-1BB ligand, and/or CD32, which allowed a loading of alpha CD3 and alpha CD28 antibodies. The costimulatory signals through CD80, 4-1BB, and CD83 ligand in low levels of IL-2 triggered an explosive ex vivo proliferation of V gamma 9V delta 2 T cells capable of secreting high levels of IL-2, IFN-gamma, and TNF-alpha. Moreover, the triple-costimulatory signals cause augmented cell viabilities for long-term growth of V gamma 9V delta 2 T cells, resulting in phenotypic changes to CD272(-)CD45RA(+) effector memory-like cells. Notably, we observed that CD83 ligand signaling is crucial to promote ex vivo expansion, survival, and cytolytic effector functions of V gamma 9V delta 2 T cells. In contrast, 4-1BB signaling is moderately important in up-regulating surface molecules on V gamma 9V delta 2 T cells. Consequently, gd T cells stimulated in the presence of triple-costimulatory signals have diverse cytolytic effector molecules, including perforin, granzyme A, granzyme B, and Fas ligand, eliciting potent cytolytic activities against tumor cells. Overall, our results provide insights into the roles of costimulatory signals in manufacturing long-lived and fully functional V gamma 9V delta 2 T cells that could be useful against cancers.</P>

아동용 창의성검사 개발 연구

문태형,김춘일 대구대학교 인문과학 예술문화연구소 1997 人文科學硏究 Vol.16 No.-

한국어 음소의 HMM모형에 관한 연구

이태호,정도일 울산대학교 1999 공학연구논문집 Vol.30 No.2

본 연구에서는 여러 개의 HMM(Hidden Markov Model) 원형을 설정하고, 각 원형에 대한 HMM 모형을 발생시켜서, 인식 실험을 통하여 각 모형에 대한 성능을 비교 평가하였다. 사용된 음성 데이터는 15명의 화자로부터 수집한 총 150개의 연속 숫자음이며, 이중 100개는 HMM 모형 발생 작업에 사용된 시험 데이터이고, 나머지 50개는 인식 작업에 사용된 시험 데이터이다. HMM 모형을 발생시키기 위해 13개의 HMM원형을 설정하였다. 본 연구에서는 두 종류의 HMM 모형 발생실험을 하였다. 하나는 음소 한 개당 한개의 모형을 발생시키는 개별 음소 모형 실험이고, 다른 하나는 유사한 특징을 가지는 음소를 묶어서 하나의 모형으로 발생시키는 집단 음소 모형 실험이다. 집단 음소 실험은 개별 음소 모형 실험에서 높은 인식률을 기록한 원형 1,2,3,4,6을 사용하여 HMM 모형을 발생하였다. 또 개별 음소 실험에서 발생된 HMM 모형의 연결을 바탕으로 단어 인식 실험을 수행하였다. 단어 인식 실험에서 사용된 개별 음소 HMM 모형 또한 개별 음소 모형 실험에서 높은 인식률을 기록한 원형 1,2,4,6에서 발생된 HMM 모형을 사용하였다. 각 실험에서 HMM 모형을 발생시키고 인식률을 산출한 결과 5 상태 좌-우 구조에서 스트림의 수가 2개이고 혼합의 수가 각각 4인 모형이 가장 우수하였다. . In this paper, the Hidden Markov Models(HMMs) which are appropriate for Korean speech are studied. A set of prototypes is prepared and a set of HMMs is generated from these prototypes. These HMMs are assessed by teh recognition test of Korean phonemes.The speech data used in this paper are the utterances of the Korean numbering system from 'hana(one)' to 'yul(ten)' which are taken from fifteen speakers. Every speaker pronounces these numbers ten times so that the total number of the sets of utterances is one hundred fifty. One hundred sets among those data are used for generating and training the HMM and the others are used for testing the HMMs. Two different types of HMM phoneme models are studied. One is the individual phoneme model. In this case, a model corresponds to a phoneme. The other is the large category model which represents a group of phonemes. Along with the phoneme recognition, the work level recognition test is performed. The HMMs for a word are constructed by linking the individual HMM phoneme models. The best result is obtained from the model which has the five states, left-right structure with two streams and four mixtures in each stream