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Objective: Interleukin-15 (IL-15) recruits and activates synovial T cells, and IL-15 plays an important role in amplifying and perpetuating inflammation in the pathogenesis of rheumatoid arthritis (RA). Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for memory T cells in the inflamed RA synovium. This study investigated the effect of IL-15 on SDF-1 production in RA fibroblast-like synoviocytes (FLS). Methods: The expressions of IL-15 and SDF-1 were determined from the synovium of patients with RA and osteoarthritis (OA) by performing immunohistochemistry. The expressions of SDF-1 was measured from the RA FLS that were cultured with IL-15 and IL-17 by real-time RT-PCR and ELISA. The SDF-1 expression was also measured, via ELISA, from the RA FLS stimulated by IL-15 together with the inhibitors of such intracellular signal molecules as phosphatidylinositol 3-kinase (PI 3-kinase, LY294002), STAT3 (AG490), MAP Kinase (PD98059), NF-κB (parthenolide) and activator protein 1 (AP-1, curcumin). Results: IL-15 and SDF-1 were mainly expressed in the RA synovium compared to that of the OA synovium. IL-15 increased the SDF-1 expressions and it, and had an additive effect with IL-17 on the SDF-1 expressions in the cultured RA FLS. The IL-15 induced increase of the SDF-1 expression in the cultured RA FLS was blocked by the inhibitors of PI 3-kinase, NF-κB and AP-1. Conclusion: The SDF-1 expression was increased in the RA synovium and it was up-regulated by IL-15 in the RA FLS through the PI 3-kinase, NF-κB, and AP-1 pathways. These results imply that the IL-15 induced increase of the SDF-1 expressions may be involved in the immunopathogenesis of RA.
LEE, JUN-HEE,CHO, MI-LA,KIM, JU-IN,MOON, YOUNG-MEE,OH, HYE-JWA,KIM, GEUN-TAE,RYU, SUN,BAEK, SEUNG-HOON,LEE, SUN-HEE,KIM, HO-YOUN,KIM, SUNG-IL The Journal of Rheumatology 2009 The Journal of rheumatology Vol.36 No.4
<B>Objective.</B><P>To examine the effect of interleukin 17 (IL-17) on the expression of Toll-like receptor (TLR)-2, 4, and 9 in collagen-induced arthritis (CIA) in mice.</P><B>Methods.</B><P>On Days 28 and 32 after induction of CIA in mice, phosphate-buffered saline (PBS group) or IL-17 (IL-17 group) was injected into both knee joints. On Day 35, mice were sacrificed. The severity of knee joint arthritis, synovial inflammation, and bone destruction was measured by a scoring system using macrography and histological analysis. Synovial expression of TLR-2, 4, 9, IL-17, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-6 was determined by real-time PCR and immunohistochemistry. Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing antibodies to cytokine, and the expression of TLR-2, 4, 9, IL-1ß, TNF-α, and IL-6 was determined by real-time RT-PCR.</P><B>Results.</B><P>In CIA mice, knee arthritis scores, synovial inflammation, bone destruction scores, and expression of synovial TLR-2, 4, and 9, IL-17, IL-1ß, TNF-α and IL-6 were higher in the IL-17 and PBS groups than in normal DBA1 mice. These variables were also significantly higher in the IL-17 group than in the PBS group. In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9, and this effect was significantly alleviated by neutralizing antibodies to IL-17, IL-1ß, and IL-6.</P><B>Conclusion.</B><P>IL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1ß and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1ß and IL-6 production are involved in the IL-17-induced aggravation of arthritis.</P>
목적: 자궁내막증은 최근에 그 빈도가 급격하게 증가되고 있으나 아직까지 병인과 치료법이 확실하게 정립되지 못하고 있는 부인과 내분비의 대표적인 질환이다. 최근 들어서 자궁내막증 환자의 불임의 원인으로 cytokine이 밀접하게 관여됨이 밝혀지고 있고 자궁내막증의 병인으로 복강내로 역류된 월경혈에 의한 복강내의 국소적 염증에 대한 개체의 반응정도와 면역체계의 변화가 중요하게 인정되고 있으나 아직까지 정확한 기전은 밝혀져 있지 않기 때문에 이에 저자는 자궁내막증 환자의 복수 내에서의 cytokine의 정량측정과 골반내 자궁내막증 병변조직에서의 cytokine mRNA의 발현 양상을 조사하여 자궁내막증 환자의 병인분석을 시도하였다. 연구방법: 자궁내막증 진단을 받고 복강경 혹은 개복 수술을 받은 30명의 환자에서 총 60개의 자궁내막증 병변이라고 의심되는 조직을 채취하여 이를 RT-PCR법을 이용하여 Cytokine 유전자의 발현양상을 조사하였다. 또한 7례의 정상대조군과 23례의 자궁내막증 환자의 복수를 ELISA법을 이용하여 정량분석을 시도하였다. 결과: 자궁내막증 환자의 복수내에서 IL-6와 IL-10의 농도는 자궁내막증의 임상적 중증도에 따라서 의미있게 증가되어 있었으나 IFN-γ, TNF-α, IL-1β, 그리고 IL-5의 농도는 정상 대조군에 비해서 변화가 없었다. 모든 예의 심부 자궁내막증 병변조직과 표재성 자궁내막증 병변조직에서 IL-1β cytokine mRNA의 발현을 볼 수 있었다. IL-5와 IL-6은 표재성 병변 12개 중에서 각각 2개의 black lesion에서만 발현을 볼 수 있었으며 IL-10은 표재성 병변에서는 12개중 2개에서 그리고 심부성 병변에서는 8개중 1개의 조직에서만 발현되었다. IFN-γ는 표재성 병변에서는 전혀 발현이 없었으나 심부성 병변에서는 8개중 4개의 조직에서 발현이 되었으며 TNF-α는 표재성 병변에서는 red 및 black 병변에서 각각 1개의 조직에서만 발현이 되었으나 심부성 병변에서는 역시 8개중 4개의 조직에서 발현이 되었다. 결론: 표재성 병변이 골반강내에 착상하여 염증성 반응이 일어날 수 있는 원인이 제공되면 IL-1β 혹은 TNF-α같은 염증성 cytokine이 분비가 되며 이로 인해 생성되는 단핵세포의 chemotactic factor에 의해 대식세포의 증가와 활성화가 이루어지고 이어서 복강내에 IL-6 등의 cytokine이 증가되며 마지막으로 여러 가지 증가된 cytokine에 대한 반대 반응으로 IL-10이 증가됨을 추정할 수가 있겠으며 이러한 가정은 앞으로 cytokine을 이용한 치료적 응용의 기초적인 연구로서 중요한 의미를 제공할 수 있다고 하겠다. Objective: The pathogenesis of endometriosis is generally accepted that retrograde menstruation and alterations in the local pelvic immune environment. This study was performed to help elucidate what kind of role various cytokines might play in the pathogenesis of endometriosis. Method: Concentrations of peritoneal fluid cytokines were compared in 7 women with normal pelvic finding and 23 women with endometriosis by enzyme-linked immunosorbent assay(ELISA). The patterns of cytokine mRNA expression in 8 ovarian endometrioma and 12 superficial pelvic endometriosis lesions were investigated by reverse transcription-polymerase chain reaction(RT-PCR) amplification method. Result: Both IL-6 and IL-10 levels in peritoneal fluid specimens with endometriosis tended to be higher than normal. However, there were no significant differences between peritoneal fluid concentrations of IFN-γ, TNF-α, IL-1β, and IL-5 of women with and without endometriosis. The levels of IL-6 and IL-10 were significantly higher in peritoneal fluid of women with severe endometriosis compared to women with mild endometriosis. IL-1β mRNA was expressed in all of 8 deep and 12 superficial endometriosis lesions. IL-5 and IL-6 mRNA were expressed in only two black lesions respectively, however, both were not expressed in the all deep lesions. Expressions of IL-10 mRNA occurred in one red and one black lesion while this was expressed in only one of the deep lesions. TNF-α mRNA was expressed in one red and one black lesion of 12 superficial lesions compared with four of the deep lesions. There was the difference between kinds of increased cytokines in the peritoneal fluid and those of expressed cytokines in the endometriotic lesions of patients with endometriosis. Conclusion: This study supports the concept that local immunologic factors may be important in the pathogenesis and pathophysiology of endometriosis. The pattern of cytokine mRNA expression of endometriotic lesions would seem to indicate that proinflammatory cytokines such as IL-1β and TNF-α are responsible for the development or progression of endometriosis.
본 연구에서는 고종시 감껍질을 열수 추출 및 초임계 유체 추출하여 아토피 피부염 증상 억제 효과를 밝히고, 항염 효능을 나타내는 기능성 소재로서의 이용 가능성을 알아보고자 하였다. 그 결과 육안 평가를 통해 피부의 홍반(erythema), 가려움과 피부의 건조상태(pruritus and dry skin), 부종과 혈종(edema and excoriation), 짓무름(erosion), 그리고 태선화(lichenification)와 같은 아토피 피부염 같은 증상이 AD 모델에서 증가하였지만, SPPE와 PPWE를 투여하였을 경우 완화되는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 피부 두께와 염증 세포의 침윤은 AD 모델에서 크게 증가하였지만, SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 혈청 중의 IgE와 IL-4의 수치를 측정한 결과, AD 모델에서 크게 증가하였으나 SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어나게 억제하는 효과를 나타내었다. 또한 RAW264.7 세포에 SPPE를 처리하였을 경우 염증매개 인자인 NO, PGE2, IL-6, IL-1β의 생성량이 유의적의로 감소하였고, PPWE의 경우 NO, PGE2, IL-1β의 생성을 억제한 반면 IL-6 생성 억제에는 영향을 나타내지 않았다. 이러한 염증 매개인자 억제 효능은 SPPE가 PPWE보다 더 뛰어나게 억제하는 것을 확인하였다. 따라서 감껍질 추출물은 아토피 피부염 증상 개선과 염증관련 질환 치료를 위한 기능성 천연물 소재로 유용하게 활용될 수 있을 것으로 판단된다. This study aimed to investigate the anti-atopic effect of hot water (PPWE) and supercritical-carbon dioxide fluid extract of persimmon peels (SPPE) on atopic dermatitis (AD)-like skin lesions in hairless mice. Histological analyses demonstrated that SPPE treatment more strongly inhibited the dermal infiltration of inflammatory cells in AD-like skin lesions than that by PPWE. Compared to PPWE, SPPE significantly decreased the dermatitis clinical score and the epidermal thickness and potently suppressed serum IgE and interleukin (IL)-4 production in hairless mice with AD. Furthermore, compared to PPWE, SPPE potently inhibited the production of nitric oxide, prostaglandin E₂, and proinflammatory cytokines such as IL-6 and IL-1β in lipopolysaccharide-stimulated RAW264.7 macrophages. These results suggested that SPPE exhibited anti-atopic dermatitis activity via the regulation of inflammatory responses.
Kim, Geun-Tae,Cho, Mi-La,Park, Young-Eun,Yoo, Wan Hee,Kim, Jung-Hee,Oh, Hye-Jwa,Kim, Dae-Sung,Baek, Seung-Hoon,Lee, Sun-Hee,Lee, Jun-Hee,Kim, Ho-Youn,Kim, Sung-Il Springer-Verlag 2010 CLINICAL RHEUMATOLOGY Vol.29 No.3
<P>The aim of this study was to investigate the expressions of Toll-like receptor (TLR) 2, TLR4, TLR9, and their correlations with the expression of cytokines that are associated with activation of CD4<SUP>+</SUP> T cells and inflammation including interferon γ (IFNγ), interleukin 4 (IL4), interleukin 17 (IL17), and tumor necrosis factor α (TNFα) in muscle tissues of patients with dermatomyositis (DM) and polymyositis (PM). The expressions of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were measured by real-time reverse transcription–polymerase chain reaction in muscle tissues from 14 patients with DM and PM (nine patients with DM, five patients with PM) and three controls. The expressions of TLR2, TLR4, and TLR9 were also localized with immunohistochemistry. The expression levels of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were significantly high in patients with DM and PM compared with those in the controls, and the expression levels of TLR4 and TLR9 had significant positive correlations with the expressions of IFNγ, IL4, IL17, and TNFα. Immunohistochemistry showed that TLR2, TLR4, and TLR9 were expressed by infiltrating cells of perimysium in DM, whereas they were expressed by infiltrating cells of endomysium in PM. These results suggest that the involvement of TLR4 and TLR9 in immunopathogenesis of DM and PM might be connected with activation of CD4<SUP>+</SUP> T cells.</P>
Kim, Dong-Kyu,Kang, Seong Il,Kong, Il Gyu,Cho, Young Hoon,Song, Seul Ki,Hyun, Se Jin,Cho, Sung Dong,Han, Sang-Yoon,Cho, Seong-Ho,Kim, Dae Woo The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.5
<P><B>Purpose</B></P><P>The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application.</P><P><B>Methods</B></P><P>A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators.</P><P><B>Results</B></P><P>The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses.</P><P><B>Conclusions</B></P><P>The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.</P>
Kim, Nayoung,Park, Young Soo,Cho, Sung-Il,Lee, Hye Seung,Choe, Gheeyoung,Kim, In Wook,Won, Yoo-Deok,Park, Ji Hyun,Kim, Joo Sung,Jung, Hyun Chae,Song, In Sung Wiley (Blackwell Publishing) 2008 Helicobacter Vol.13 No.4
<P>BACKGROUND AND AIM: The prevalence of gastric cancer and Helicobacter pylori infection is unacceptably high in Korea. This study was performed to evaluate the prevalence of atrophic gastritis (AG) and intestinal metaplasia (IM) and to identify their risk factors with respect to H. pylori virulence factors, and environmental and host factors, in Korean population without significant gastroduodenal disease. METHODS: The study cohort consisted of 389 subjects (> or = 16 years). AG and IM were scored histologically using the Sydney classification in the antrum and body, respectively. Prevalences and bacterial factors (i.e. cagA, vacA m1, and oipA), environmental factors (i.e. smoking and alcohol), and host factors (i.e. genetic polymorphisms of IL-1B-511, IL-1RN, TNF-A-308, IL-10-592, IL-10-819, IL-10-1082, IL-8-251, IL-6-572, GSTP1, p53 codon 72, and ALDH2) were evaluated. RESULTS: Prevalences of AG in the antrum and body were 42.5% and 20.1%, and those of IM were 28.6% and 21.2%, respectively. The presences of AG and IM were significantly higher in H. pylori-positive than in the H. pylori-negative subjects. Multivariate analysis showed that the risk factors for AG were H. pylori infection, age > or = 61 years, and cagA and vacA m1 positivity. For IM the risk factors were H. pylori infection, age > or = 61 years, a smoking history (rather than current smoking), strong spicy food, occupation (unemployed or nonprofessional vs. professional), and the presence of IL10-592 C/A as opposed to A/A. In addition, IL6-572 G carrier was found to have a protective effect against IM development as compared with C/C. CONCLUSION: H. pylori infection was most important risk factor of AG and IM. Bacterial factors were found to be important risk factor for AG but environmental and host factors were more important for IM.</P>
Jang, You-Jee,Park, Jae-Il,Jeong, Seong-Eun,Seo, You-Mi,Dam, Phuong T. M.,Seo, Young-Woo,Choi, Bum-Chae,Song, Sang-Jin,Chun, Sang-Young,Cho, Moon-Kyoung Commonwealth Scientific and Industrial Research Or 2017 Reproduction, fertility, and development Vol.29 No.12
<P> The aim of the present study was to examine the regulation of interleukin (IL)-11 expression, as well as the role of IL-11, during ovulation in gonadotropin-primed immature rats. Injection of equine chorionic gonadotropin (eCG), followed by human CG (hCG) to induce superovulation stimulated expression of the Il11 gene in theca cells within 6 h, as revealed by northern blot and in situ hybridisation analyses. Real-time reverse transcription-polymerase chain reaction analysis showed that the IL-11 receptor, α subunit gene was expressed in granulosa and theca cells and that injection of hCG had no effect on its expression. IL-11 protein expression was stimulated in theca cells by hCG. LH-stimulated increases in Il11 mRNA levels in cultured preovulatory follicles were inhibited by protein kinase A and mitogen-activated protein kinase kinase inhibitors. Toll-like receptor (TLR) 2 and TLR4 were detected in preovulatory follicles, and the TLR4 ligand lipopolysaccharide, but not the TLR2 ligand Pam3Cys, increased Il11 mRNA levels in theca cells, but not in granulosa cells. Treatment of preovulatory follicles with IL-11 stimulated progesterone production and steroidogenic acute regulatory protein (Star) gene expression. Together, these results indicate that IL-11 in theca cells is stimulated by mitogen-activated protein kinase signalling and TLR4 activation, and increases progesterone production during ovulation. </P>
본 실험에서는 동양에서 예로부터 민간요법이나 한방에서 주로 많이 쓰여지고 있는 8가지 종류의 한약재에 대해서 면역억제제로써 사용 가능성을 실험하였다. 그 결과 당귀, 산사, 어성초, 오가피, 황기의 추출물은 동종항원에 반응하는 순수분리 T세포의 증식을 농도 의존적으로 억제시켰다. 또한 이들 T세포의 증식에 있어서 필수적인 IL-2를 포함한 cytokine 즉, IL-2, IL-4, IL-10, IFN-γ의 생산량은 대조군에 비해 실험군에서 유의한 차이가 없었고 특히 T세포 증식에 필수적인 IL-2의 생산량의 변화가 거의 없었다. 이는 한약재에 의한 T세포의 증식억제 효과가 T세포증식에 필수적인 IL-2의 생산량을 억제하기 때문에 일어나는 결과가 아님을 알 수 있었다. 그리고 T세포의 살세포작용 억제를 직접적으로 측정하기 위하여 세포내 LDH의 양을 조사한 결과 모든 대조군에서 50%이상의 살세포작용 억제가 일어났고, 그중 특히 오가피와 황기에서는 100% 살세포작용 억제가 일어났다. 따라서 본 실험에 사용된 당귀, 산사, 어성초, 오가피, 황기 등의 5가지 약재가 부작용 없는 면역억제로써 사용 가능성이 높은 것으로 생각된다. In this experiment, we showed the immunosuppressive effects of herbal plant extracts on the alloantigen reactive proliferation and cytotoxicity. The extracts of Angelica gigas, Crataegus pinnatifida, Houttuynia cordata, Acanthopanax sessiliflorum and Astragalus membranaceus markedly suppressed on the pro- liferation of primary T cells stimulated with allogeneic spleen cells in a dose-dependent manner. The production of IL-2, IFN-γ, IL-4 and IL-10 in the alloreactive primary T cells showed no significant difference in the presence or absence of herbal plants extracts. Also the result of mixed lymphocyte reaction (MLR)-induced cytotoxic T lymphocyte (CTL) showed what is above a certain point 50% inhibition. Specially, the extracts of Acanthopanax sessiliflorum and Astragalus membranaceus com- pletely suppressed the killing activity of CTL. Theses results suggest that the extracts of 5 herbal plants can be used as immunosuppressive agents.
Increasing importance is being given to the stimulation of Th1 response in cancer immunotherapy because its presence can shift the direction of adaptive immune responses toward protective immunity. Based on chemokine receptor expression, CXCR3+CCR4-CD4+ T cells as Th1-type cells were investigated its capacity in monocyte-derived dendritic cell (DC) maturation and polarization, and induction of antigen specific cytotoxic T lymphocytes (CTL) in vitro. The levels of IL-4, IL-5 and IL-10 were decreased to the basal level compared with high production of IFN-γ, TNF-α, and IL-2 in CXCR3+CCR4-CD4+ T cells stimulated with anti-CD3 and anti-CD28 antibodies. Co-incubation of activated CD4+ or CXCR3+CCR4-CD4+ T cells with DC (CD4+/DC or CXCR3+CD4+/DC, respectively) particularly up-regulated IL-12 and CD80 expression compared with DC matured with TNF-α and LPS (mDC). Although there was no significant difference between the effects of the CXCR3+CCR4-CD4+ and CD4+ T cells on DC phenotype expression, CXCR3+CD4+/DC in CTL culture were able to expand number of CD8+ T cells and increased frequencies of IFN-γ secreting cells and overall cytolytic activity against tumor antigen WT-1. These results demonstrated that the selective addition of CXCR3+ CCR4- CD4+ T cells to CTL cultures could enhance the induction of CTLs by DC in vitro, and implicated on a novel strategy for adoptive T cell therapy. Increasing importance is being given to the stimulation of Th1 response in cancer immunotherapy because its presence can shift the direction of adaptive immune responses toward protective immunity. Based on chemokine receptor expression, CXCR3+CCR4-CD4+ T cells as Th1-type cells were investigated its capacity in monocyte-derived dendritic cell (DC) maturation and polarization, and induction of antigen specific cytotoxic T lymphocytes (CTL) in vitro. The levels of IL-4, IL-5 and IL-10 were decreased to the basal level compared with high production of IFN-γ, TNF-α, and IL-2 in CXCR3+CCR4-CD4+ T cells stimulated with anti-CD3 and anti-CD28 antibodies. Co-incubation of activated CD4+ or CXCR3+CCR4-CD4+ T cells with DC (CD4+/DC or CXCR3+CD4+/DC, respectively) particularly up-regulated IL-12 and CD80 expression compared with DC matured with TNF-α and LPS (mDC). Although there was no significant difference between the effects of the CXCR3+CCR4-CD4+ and CD4+ T cells on DC phenotype expression, CXCR3+CD4+/DC in CTL culture were able to expand number of CD8+ T cells and increased frequencies of IFN-γ secreting cells and overall cytolytic activity against tumor antigen WT-1. These results demonstrated that the selective addition of CXCR3+ CCR4- CD4+ T cells to CTL cultures could enhance the induction of CTLs by DC in vitro, and implicated on a novel strategy for adoptive T cell therapy.