• Restorative Dentistry and Endodontics
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• 제27권1호
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• pp.1-11
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• 2002

Immune responses associated with bacterial infection involve various inflammatory cells. Clinical symptoms and pathologic features are particularly influenced by the predominant cells Among inflammatory cells, T cells have the heterogenity. T cells may develop into the mature cells expressing the cell surface markers with different functions and T helper cells are categorized into Th1 and Th2 cells based on their different patterns of cytokine production. The objective of this study was to investigate the change of expression of surface markers on T cells and the Th1/Th2 immune response in pulpal inflammation associated with specific bacteria. We experimentally induced pulpal inflammation in rat incisors by drilling without coolant and innoculated with Streptococcus mutans (S.M. group), Porphyromonas endodontalis (P.E. group), or only sterile cotton (control group). After 1, 2, and 5 days, mandibular incisors were extracted and the pulp tissues were extirpated The expressions of IL-2 recepters (CD25) and ICAM-1 (CD54) on CD4+ and CD8+ cells in the pulps were determined using a flow cytometer, and the concentration of IL-2, IFN-$\gamma$ and IL-4 was measured by enzyme-linked immunosorbent assay. The results were as follows: 1 In the S.M. group, CD4+ cells were more increased at 2nd day than 1st day and in the P.E. group, CD8+ cells were more increased at 2nd day than 1st day. 2. The percentages of CD4+, CD4+25+ and CD4+54+ cells were decreased in the pulp tissues at 5th day after irritation in all groups. 3. The ratios of CD4+/CD8+, CD4+/CD4+25+ and CD4+/CD4+54+ in the pulps at 2nd day after irritation by P. endodontalis were significantly lower than the other groups. 4. The higher concentrations of IFN-$\gamma$ than IL-4 in the pulps at 2nd day after irritation by P. endodontalis showed that T helper 1 reaction were predominant in the early stage of the pulpal inflammation induced by P. endodontalis. 5. The higher concentrations of IL-4 than IFN-$\gamma$ in the pulps at 1st day and 5th day after irritation by S. mutans were measured but the differences were not significant.

• 대한핵의학회지
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• 제25권1호
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• pp.110-116
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• 1991

To elucidate alteration of peripheral T cell subsets in thyroid tumors, the author enumerated T cell subsets in periphral blood by indirect immunofluorescent method, using monoclonal antibodies (CD3, CD4 and CD8) in 17 cases of thyroid cancer, 12 cases of thyroid adenoma, and 16 cases of adult healthy subjects as controls. Diagnoses were confirmed histopatologically in thyroid cancer and adenoma, and were established on the basis of commonly accepted clinical and biochemical criteria in Hashimoto's thyroiditis. The blood was drawn from veins of the patients and control subjects in Pusan National University Hospital during the period of January to October 1990. The results obtained were summarized as follow: 1) The percentage of CD3+ cells was significantly decreased in thyroid cancer as compared with healthy subjects. 2) The percentage of CD4+ cells was not different among thyroid cancer, thyroid adenoma, Hashimoto's thyroiditis and control subjects each other. 3) The percentage of CD8+ cells was significantly decreased in thyroid cancer as compared with adult healthy subjects, and tended to be decreased as compared with thyroid adenoma and Ha-shimoto's thyroiditis. 4) The CD/CD8 ratio was significantly increased in thyroid cancer as compared with control subjects, and tended to be increased as compared with thyroid adenoma and Hashimoto's thyroiditis. On the basis of the results, it can be suggested that the immunodysfunction may be due to decreased soppressor/cytotoxic T cells in thyroid cancer.

• IMMUNE NETWORK
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• 제23권1호
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• pp.9.1-9.15
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• 2023

Cancer immunotherapies continue to face numerous obstacles in the successful treatment of solid malignancies. While immunotherapy has emerged as an extremely effective treatment option for hematologic malignancies, it is largely ineffective against solid tumors due in part to metabolic challenges present in the tumor microenvironment (TME). Tumor-infiltrating CD8⁺ T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T-cell recruitment to the tumor site and hyporesponsive effector functions via T-cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8⁺ T-cell activation, migration, effector functions, and persistence in tumors. Therefore, targeting the mitochondrial metabolism of adoptively transferred T cells has the potential to greatly improve the effectiveness of cancer immunotherapies in treating solid malignancies.

• 미생물학회지
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• 제47권4호
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• pp.342-347
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• 2011

인체의 바이러스 감염 방어기전에서 T 림프구는 중요한 역할을 한다. 하지만, 만성 C형 간염 바이러스의 일차적 복제장소인 간염 환자의 간에서 분리된 HCV 특이 T 림프구는 심각한 기능결핍을 보인다. 이러한 T 림프구 기능결핍의 이유로는 PD-1, CTLA-4 등 면역억제 물질의 발현, 또는 간에서 특이적으로 유도되는 면역내성(immune tolerance)이 있으나, 간세포(hepatocytes)와 HCV 특이 T 림프구의 상호작용에 대해서는 명확하게 확립되어 있지 않다. 따라서 본 연구에서는 HLA(human leukocyte antigen) A2+ 간암세포주(human hepatoma cell line; huh7.5)가 항원제시(antigen presentation)를 통해 효과적으로 HCV 특이 T 림프구를 활성화시키며 간암세포주(huh7.5) 표면의 PD-L (program death ligand) 1 발현은 T림프구의 활성을 감소시켜 면역조절의 가능성이 있음을 시사하였다. 또한, HCV 특이 tetramer 반응은 T 림프구의 과도한 활성으로 자기사멸(apoptosis)의 경로에 있음을 caspase 3 활성으로 확인하였고, 역시 PD-L1의 발현이 T 림프구를 자기사멸(apoptosis)로부터 구제하여 caspase 3 활성이 감소하는 것을 확인하였다. 이는 PD-L1과 간성(liver) T 림프구 표면의 PD-1 결합이 T 림프구의 자기사멸을 막고, 또한 그 기능을 회복시켜 만성 C형 간염 치료에 응용될 수 있음을 시사한다.

• IMMUNE NETWORK
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• 제23권2호
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• pp.17.1-17.16
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• 2023

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8⁺ and CD4⁺ T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8⁺ T cell responses were significantly higher than CD4⁺ T cell responses. CD8⁺ T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4⁺ T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×105 CD8⁺ or CD4⁺ T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.

• Molecules and Cells
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• 제37권5호
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• pp.365-371
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• 2014

Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed.

• Natural Product Sciences
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• 제13권2호
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• pp.123-127
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• 2007

We investigated effect of small black soybean fraction (SBSF) T cell-mediated responses for tumor surveillance and proliferation in leukemia cells in vitro. Each SBSF butanol fraction (SBSFBu) and SBSF chloroform fraction (SBSFCh) was administered p.o. once a day far 21 days in BALB/c mice and then levels of serum cytokines and subpopulation of lymphocytes were measured. Moreover, SBSF fraction was treated into the cultured various cell lines for proliferation in leukemia cell lines, NO production by RAW264.7 cells, and expression of p53 gene in U937 leukemia cells. These results showed that SBSFBu increased levels of serum IL-4but not IL-2 and IFN-${\gamma}$, and increased expression of CD4$^+$ T cells and CD8$^+$ T cells in splenocytes in vivo, while SBSFCh increased levels of serum IL-2 and IFN-${\gamma}$ but decreased IL-4, and increased CD8$^+$ T cells but not CD4$^+$ T cells. Moreover, both of SBSFBu and SBSFCh inhibited proliferation of HL60, U937, and L1210 leukemia cell lines in a dose-dependent manner, up-regulated NO production by RAW264.7 cells in a dose-dependent manner, and enhanced expression of p53 gene in U937 leukemia cells. Our findings indicate that SBSFBu and SBSFCh may enhance T cell-dependent immune responses, and that both of SBSFBu and SBSFCh may inhibit proliferation of leukemia cells by up-regulation of NO production and expression of p53 gene.

• Clinical and Experimental Reproductive Medicine
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• 제37권3호
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• pp.231-237
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• 2010

목 적: 반복적 유산 또는 반복적 착상실패 환자의 T 림프구의 Th1 면역반응 정도를 알아보고, T 림프구 활성 정도를 분석하고자 하였다. 연구방법: 반복적 유산 및 반복적 착상실패를 경험한 37명의 환자를 연구군으로 설정하고, 유산이나 불임의 병력이 없이 정상분만의 경력이 있는 11명의 가임 여성을 대조군으로 모집하였다. 유세포분석기를 이용하여, 이들의 말초혈액 중 T helper 세포 내 TNF-$\alpha$와 INF-$\gamma$ 및 IL-10의 발현도를 측정하고 Th1/Th2 세포 비율 (TNF-$\alpha$/IL-10 및 INF-$gamma$/IL-10 발현도)을 계산하여 Th1 면역반응의 우세 정도 및 T 림프구의 활성도를 분석하였으며, 활성 표지자인 CD154와 CD69 발현 정도를 비교하였다. 결 과: 연구군의 평균연령은 $35.3{\pm}4.3$세였으며, 이들에서 T helper cell 내 TNF-$\alpha$/IL-10의 발현 비율이 대조군에 비해 유의하게 높았고 ($42.1{\pm}2.3$ vs. $28.7{\pm}2.7$, p=0.002), CD154와 CD69의 발현율 또한 대조군에 비해 전반적으로 높았다. CD154의 경우, T helper cell ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038)과 T suppressor cell ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) 모두에서 유의하게 높은 발현을 보인 반면, CD69의 경우, 전체 T 림프구 ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046)와 T suppressor cell ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035)에서 통계적으로 높은 발현을 확인할 수 있었다. 결 론: 반복적 유산 및 반복적 착상실패를 보이는 여성에서 T 림프구의 활성도와 Th1 면역반응이 증가하였으며 이는, 이들 여성에서 활성화된 T 림프구가 Th1 면역반응을 유도하여 초기 임신의 유지와 착상에 좋지 않은 영향을 미치기 때문으로 생각된다.

• Clinical and Experimental Pediatrics
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• 제51권5호
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• pp.492-499
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• 2008

목 적 : H. pylori의 감염은 세균의 병독 인자, 숙주 인자, 환경 인자가 복합적으로 작용하여 다양한 위장관 병변을 일으킨다. H. pylori의 병리 기전으로 지금까지는 주로 세균의 병독성에 초점을 맞추었으나 최근에는 숙주의 위점막 면역반응이 주목을 받고 있다. 소아는 술, 담배, 약물과 같은 환경 인자의 영향이 적어 연구에 적합한 대상이며 감염 초기를 반영한다는 측면에서 중요한 의의가 있음에도 불구하고 소아에서 위점막 면역반응에 관한 연구가 거의 없다. 이에 H. pylori 감염 소아에서 위점막 림프구를 분석하여 소아에서 H. pylori 감염으로 인한 국소 면역반응의 특징을 알아보고자 하였다. 방 법 : H. pylori 양성 소화궤양군 10명, H. pylori 양성 위염군 15명, H. pylori 음성 대조군 20명에서 얻은 위전정부 생검조직에서 hematoxylin-eosin 염색과 modified Giemsa 염색을 시행하여 개정된 시드니 체계에 따라 위염의 정도를 점수화하였다. 위점막에서 림프구 면역표현형을 알기 위해 CD3, CD4, CD8 T세포와 CD20 B세포에 대한 면역조직화학염색을 시행하였으며 점막 고유층에서는 400배 고배율 현미경 하에서 $0.0625m^2$ 당 양성 림프구 수를 기록하였고, 상피세포 내에서는 100개 상피세포 당 양성 림프구 수를 기록하였다. 결 과 : 림프구 침윤은 점막 고유층에서 상피세포 내보다 확연히 많았다. 점막 고유층에서 H. pylori 양성군에서 대조군에 비해 CD3, CD4, CD8 T세포와 CD20 B세포가 유의하게 증가하였고(P<0.01) H. pylori 양성 소화궤양군은 위염군과 달리 대조군에 비해 CD8 T세포가 유의하게 증가하였다(P<0.01). 한편, 상피세포 내에서는 H. pylori 양성 소화궤양군과 위염군 모두 대조군에 비해 CD4 T세포가 유의하게 증가하였다(P<0.01). H. pylori의 밀도, 다핵형 중성구의 활동성, 만성 염증 정도와 림프구 수는 점막 고유층에서 상피세포 내보다 더 밀접한 상관관계가 있었다. 결 론: H. pylori에 감염된 소아의 국소 면역반응은 주로 위점막 고유층에서 일어나며 T세포와 B세포가 함께 관여하였다. H. pylori 양성 소화궤양군에서 점막 고유층의 CD8 T세포가 유의하게 증가하여 임상질환과 점막면역의 연관성을 추정할 수 있었다. 향후 H. pylori 감염에서 국소 면역반응으로 야기되는 점막 손상, 연령과 인종에 따른 차이, 임상질환과의 연관성 등에 대하여 더 많은 연구가 이루어져야 할 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5909-5913
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• 2012

Aims: We aimed to analyze the phenotype of tumor-infiltrating lymphocytes (TILs) and non-tumor infiltrating lymphocytes (NILs) in HCC and non-tumor tissues, and evaluate relationships between changes in these cells and the prognosis of HCC. Methods: Lymphocytes were isolated from HCC and corresponding non-tumor tissues and tested by flow cytometry. For comparison, clinical parameters were analyzed. Results: Compared with the non-tumor tissue, tumor tissue had a lower intensity of NK, NKT andCD8+T cell infiltration. TILs had higher intensity of CD4+CD25+Foxp3+regulatory T cell (Treg cells) infiltration compared with that in NILs. The prevalence of Treg cells was associated with fewer CD8 + T lymphocytes in the HCC immune microenvironment. The frequencies of NK cells and CD8+T cells in TILs of HCC patients with metastasis less than 12 months were lower than those without metastasis. However, the frequency of Treg cells was higher than those without metastasis. Conclusion: These results suggest that the frequencies of CD8+T, NK and NKT cells as well as Treg cells in the tumor tissue of HCC are significantly associated with patient survival, and could be applied as predictive indicators for HCC prognosis.