• IMMUNE NETWORK
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• 제7권4호
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• pp.173-178
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• 2007

Background: We studied the role for expression of CD40 and CD40L by CD4 and CD8 T cells in the generation of CD8 T cell response to minor histocompatibility antigen, H60. H60 is a cellular antigen to which CD8 responses require CD4 T cell help. Methods: CD40- or CD40L-deficient mice were adoptively transferred with normal CD4 or CD8 T cells or with memory CD4 or CD8 T cells, and were immunized with male H60 congenic splenocytes to induce CD8 T cell response to H60. Peripheral blood CD8 T cell from the immunized mice were stained with the H60 tetramer. Results: CD8 T cell response to H60 was not induced in both CD40- and CD40L-deficient mice. Adoptive transfer of $CD40^{+/+}$ CD8 T cells into CD40-deficient mice did not compensate the defect in inducing CD8 T cell response to H60, while the H60-specific CD8 T cells were activated in the CD40-deficient mice that were adoptively transferred with $CD40^{+/+}$ CD4 T cells. Adoptive transfer of $CD40L^{+/+}$ CD4 T cells into CD40L-deficient mice induced primary CD8 T cell response for H60 and the presence of $CD40L^{+/+}$ CD4 T cells was required even for memory CD8 T cells response to H60. Conclusion: Our results suggest that the CD40-CD40L interaction mediates the delivery of CD4 T cell help to naive and memory H60-specific CD8 T cells. While the expression of CD40L by CD4 T cells is essential, signaling through CD40 on CD8 T cells is not required for the induction of CD8 T cell response to H60.

• IMMUNE NETWORK
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• 제23권5호
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• pp.41.1-41.21
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• 2023

CD4 and CD8 T cells are key players in the immune response against both pathogenic infections and cancer. CD4 T cells provide help to CD8 T cells via multiple mechanisms, including licensing dendritic cells (DCs), co-stimulation, and cytokine production. During acute infection and vaccination, CD4 T cell help is important for the development of CD8 T cell memory. However, during chronic viral infection and cancer, CD4 helper T cells are critical for the sustained effector CD8 T cell response, through a variety of mechanisms. In this review, we focus on T cell responses in conditions of chronic Ag stimulation, such as chronic viral infection and cancer. In particular, we address the significant role of CD4 T cell help in promoting effector CD8 T cell responses, emerging techniques that can be utilized to further our understanding of how these interactions may take place in the context of tertiary lymphoid structures, and how this key information can be harnessed for therapeutic utility against cancer.

• IMMUNE NETWORK
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• 제16권2호
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• pp.126-133
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• 2016

Unlike conventional T cells, innate CD8 T cells develop a memory-like phenotype in the thymus and immediately respond upon antigen stimulation, similar to memory T cells. The development of innate CD8 T cells in the thymus is known to require IL-4, which upregulates Eomesodermin (Eomes). These features are similar to that of virtual memory CD8 T cells and IL-4-induced memory-like CD8 T cells generated in the peripheral tissues. However, the relationship between these cell types has not been clearly documented. In the present study, IL-4-induced memory-like CD8 T cells generated in the peripheral tissues were compared with innate CD8 T cells in terms of phenotype and function. When an IL-4/anti-IL-4 antibody complex (IL-4C) was injected into C57BL/6 mice daily for 7 days, the Eomes^hiCXCR3⁺ CD8 T cell population was markedly increased in the peripheral lymphoid organs and blood. These cells were generated from naïve CD8 T cells or accumulated via the expansion of pre-existing CD44^hiCXCR3⁺ CD8 T cells. Initially, the majority of these CXCR3⁺ CD8 T cells expressed low levels of CD44, which was followed by the conversion to the CD44^hi phenotype. This conversion was associated with the acquisition of enhanced effector function. After discontinuation of IL-4C treatment, Eomes expression levels gradually decreased in CXCR3⁺ CD8 T cells. Taken together, the results of this study demonstrate that IL-4-induced memory-like CD8 T cells generated in the peripheral lymphoid tissues are phenotypically and functionally similar to the innate CD8 T cells generated in the thymus.

• 대한한방내과학회지
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• 제25권4호
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• pp.117-128
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• 2004

Objectives : To examine the effects of Gojineumja on white rats which deteriorated immunity caused by Methotrexate(MTX), first of all, MTX was fed to the rats once a day for 4 day. Methods : After the immune response of the rats are deteriorated, dried extracts of Gojineumja(GJE) mixed in water was fed to the white rats once a day for l4days. The next conclusion was made by examining the rates of B-cells and T-cells of the peripheral blood and the changes in rates of CD4+ T-cells and CD8+ T -cells of the blood sampled from the spleen and peripheral region. Especially the count of CD3+ CD4+ T-cells of the peripheral blood and the count of CD3+ CD4+ T-cells of the spleen the count of CD4+/ CD8+ T-cell of the peripheral blood and the spleen proved the significant effect of increasing immune responses statistically. Results :(1) The following are the summary of the results. (2) The percentage of B lymphocyte of peripheral blood was increased significantly in GJE group as compared with control group. (3) The percentage of CD3+ CD4+ T-cell of peripheral blood was increased significantly in GJE group as compared with control group. (4) The percentage of CD3+ CD8+ T-cell of peripheral blood was not different statistically. (5) The percentage of CD4+/ CD8+ T-cell of peripheral blood was increased significantly in GJE group as compared with control group. (6) The percentage of CD3+ CD4+ T-cell of spleen was increased significantly in GJE group as compared with control group. (7) The percentage of CD3+ CD8+ T-cell was not different statistically. (8) The percentage of CD4+ /CD8+ T-cell was not different statistically. Conclusions : Gojineumja has an effect of increasing immune responses on white rats with deteriorated immunity caused by MTX.

• IMMUNE NETWORK
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• 제9권4호
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• pp.127-132
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• 2009

Background: Toll-like receptors (TLRs) play a fundamental role in innate immunity through their capacity to recognize pathogen-associated molecular patterns. Also, TLRs that are expressed in T cells are reported to function as co-stimulatory receptors. However, the functional capacity of TLRs on CD4 T and CD8 T cells has not been directly compared. Here we compared CD4 and CD8 T cell responses to TLR2 ligand plus TCR-mediated stimulation. Methods: TLR2 expression was analyzed on T cell subsets under naive and alloantigen-primed conditions. We analyzed the effects of TLR2 co-stimulation on proliferation and survival of T cell subsets in vitro when stimulated with soluble anti-CD3 in the presence or absence of synthetic ligand $Pam_3CSK_4$. Results: TLR2 expression on CD8 T cells was induced following activation; this expression was much higher than on CD4 T cells. Thus, the molecule was constitutively expressed on Listeriaspecific memory CD8 T cells. Based on these expression levels, proliferation and survival were markedly elevated in CD8 T cells in response to the TLR2 co-stimulation by $Pam_3CSK_4$ compared with those in CD4 T cells. Conclusion: Our data show that TLR2 co-stimulation is more responsible for proliferation and survival of CD8 T cells than for that of CD4 T cells.

• Clinical and Experimental Pediatrics
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• 제51권12호
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• pp.1336-1341
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• 2008

목 적: 본 연구의 목적은 사람의 동종 조혈모세포이식에서 공여자의 이식편과 환자의 이식 후 말초혈액에서 $CD4^+CD25^+$ T 세포 분획의 분포를 알아보고 급성 이식편대숙주병(GVHD)과 연관성을 알아보고자 하였다. 방 법: 동종 조혈모세포이식을 시행 받은 17명의 소아를 대상으로 하였다. 공여자의 이식편과 이식 받은 환자의 이식 후 말초혈액으로부터 얻은 검체를 유세포 분석(flow cytometry)하였다. 공여자의 이식편과 이식 후 1개월과 3개월에 환자의 말초혈액 내 $CD4^+CD25^+$ T 세포의 분획과 절대 세포수를 알아보았다. 결 과: 공여자의 이식편 내 $CD4^+CD25^+$ T 세포의 분획은 급성 GVHD 발생군과 비발생군에서 각각 0.90%, 1.06%이었으며 차이가 없었다(P=0.62). 이식편 내 $CD4^+CD25^+$ T세포의 절대수는 급성 GVHD 발생군과 비발생군이 각각 $6.18{\times}10^5/kg$와 $25.85{\times}10^5/kg$으로 급성 GVHD 비발생군이 발생군보다 많은 경향을 보였으나 유의성은 없었다(P=0.09). 급성 GVHD 비발생군의 말초혈액 $CD4^+CD25^+$ T 세포는 이식 후 1개월에 2.11%, 3개월에 1.43%로 유의하게 감소하였으나(P=0.028), 급성 GVHD 발생군의 말초혈액 내 $CD4^+CD25^+$ T 세포는 이식 후 1개월과 3개월에 각각 2.47%와 2.30%로 유의한 차이가 없었다(P=0.50). 결 론: 본 실험을 통하여 저자들은 공여자의 이식편 내 $CD4^+CD25^+$ T세포의 분포와 이식 후 환자의 급성 GVHD의 관계에 대한 유의성은 검증할 수 없었으며 이식 후 환자의 말초혈액 내 $CD4^+CD25^+$ T 세포에는 조절 T세포보다 GVHD와 연관된 활성화된 T세포의 분획이 더 클 것으로 사료되나 추가적인 조절 T세포의 표지자를 이용한 검증이 필요할 것으로 사료된다.

• 대한의생명과학회지
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• 제1권1호
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• pp.27-35
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• 1995

HIV감염자는 질병의 진전에 무관하게 감염 후의 경과 시기에 따라서 CD4 T림프세포등 각종 면역상태를 나타내는 표지가 변한다 따라서 HW감염자의 질병진전을 예보하기 위하여서는 정기적으로 CD4등 각종표지를 측정하여 감염자의 질병상태를 monitoring하게 된다. 그러나 이러한 수치를 감염자관리에 적용하기 위하여서는 우리나라 일반인의 정상치를 파악하여 이를 지표로 해야 하므로 국내정상인의 각종 면역치에 대한 조사가 요구된다. 현재의 기준으로는 500이하로 떨어질 때에는 예방차원에서 AZT를 복용하게 되며 200이하로 떨어지면 질병의 유무에 관계없이 환자로 관리하게 된다. 본 연구에서는 한국인 185명의 감염자와 140명의 비감염자에 대하여 정기적으로 CD4 및 CD8T 림프세포와 CD4/CD8비를 측정하였다. 시험은 Flow cytometer(Facstar)를 이용하여 각각의 CD 분자에 대한 모노크로날 항체를 이용하여 2중혈광색소 염색방법으로 측정 하였다. HIV감염자의 CD4-T림프세포 절대수 및 백분율은 각각 462 및 18.2%이었는 반면, CD8의 수치는 1,170 및 47.0%이었다. 또한 CD4/CDB비는 0.43이었다. 이와는 대조적으로 비감염자의 경우, 한국인의 CD4의 평균 세포수는 886, 백분율은 32.9%이었으며, CD8 세포수는 730, 백분율은 26.8 그리고 CD4/CD8비는 1.31이었다. 외국인과 한국인과의 면역지표 수치를 비교하였을 때에 CD4세포수와 백분율, CD8의 백분율에서는 현저한 차이가 없었으나 외국인 비감염자의 경우 CD4백분율이 43.6%, CD8 T림프세포의 절대수가 560으로 한국인과 약간의 차이가 있었다. 따라서 HIV 감염자관리를 위한 면역지표측정시험에서의 각종수치의 정확한 해석을 위하여서는 한국인 비감염자수치를 고려해야할 것으로 판단된다.

• Clinical and Experimental Pediatrics
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• 제54권4호
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• pp.157-162
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• 2011

Purpose: Exaggerated pro-inflammatory reactions during the acute phase of Kawasaki disease (KD) suggest the role of immune dysregulation in the pathogenesis of KD. We investigated the profiles of T regulatory cells and their correlation with the clinical course of KD. Methods: Peripheral blood mononuclear cells were collected from 17 KD patients during acute febrile and subacute afebrile phases. T cells expressing CD4, CD25, and Foxp3 were analyzed using flow cytometry, and the results were correlated with the clinical course of KD. Results: The percentage of circulating $CD4^+CD25^{high}Foxp3^+$ T cells among $CD4^+$ T cells was Significantly higher during the subacute afebrile phase than during the acute febrile phase ($1.10%{\pm}1.22%$ vs. $0.55%{\pm}0.53%$, P=0.049). Although levels of $CD4^+CD25^{low}Foxp3^+$ T cells and $CD4^+CD25^-Foxp3^+$ T cells were only slightly altered, the percentage of $CD4^+CD25^+Foxp3^-$ T cells among $CD4^+$ T cells was significantly lower during the subacute afebrile phase than during the acute febrile phase ($2.96%{\pm}1.95%$ vs. $5.64%{\pm}5.69%$, P=0.036). Consequently, the ratio of $CD25^{high}Foxp3^+$ T cells to $CD25^+Foxp3^-$ T cells was higher during the subacute afebrile phase than during the acute febrile phase ($0.45%{\pm}0.57%$ vs. $0.13%{\pm}0.13%$, P=0.038). Conclusion: Decreased $CD4^+CD25^{high}Foxp3^+$ T cells and/or an imbalanced ratio of $CD4^+CD25^{high}Foxp3^+$ T cells to $CD4^+CD25^+Foxp3^-$ T cells might playa role in KD development. Considering that all KD patients were treated with intravenous immunoglobulin (IVIG), recovery of $CD4^+CD25^{high}Foxp3^+$ T cells during the subacute afebrile phase could be a mechanism of IVIG.

• 대한소아치과학회지
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• 제35권4호
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• pp.597-606
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• 2008

본 연구는 TNFR family인 CD137 및 RANK, 파골세포의 CD137L와 T 세포의 RANKL 간의 역신호에 의한 이들 세포 의 역할을 알아보고자 하였다. 이에 RANKL 및 CD137L 자극으로 유도되는 역신호 전달에 의한 T 세포 활성과 파골세포분 화에 미치는 영향을 규명하고자 웅성 생쥐의 골수세포와 T 세포를 공동배양하여 다음과 같은 결과를 얻었다. 1. 생쥐 단핵세포주 및 골수유도 단핵전구세포에서 CD137L이 발현되며, CD137L 단클론 항체로 자극을 주었을 경우 파 골세포 표지단백질인 TRAP 양성 파골세포의 형성이 억제되었다. 2. 활성화된 $CD4^+$ 및 $CD8^+$ T 세포에서 RANKL을 발현하였으며 RANKL의 유사 수용체인 OPG 재조합 단백질을 처리 하여 $CD4^+$ 및 $CD8^+$ T 세포의 세포증식이 억제되었다. 이 연구의 결과는 CD137 자극에 의한 T 세포활성 및 RANK 자극에 의한 파골세포분화 및 활성이 각각 수용체에 결합하 는 라이겐드의 역신호에 의해 억제되었는데, 이는 파골세포와 T 세포의 과도한 활성을 제어하는 생체의 항상성조절에 관여하 는 기전으로 생각된다.

• 혜화의학회지
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• 제17권1호
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• pp.67-74
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• 2008

Objective: The purpose of this research is to examine the effects of Mahaenggamseok-tang-gagambang (MGTG) on CD3+ T cells, CD4+ T cells and CD8+ T cells in ovalbumin (OVA)-induced asthmatic mice. Methods: C57BL/6 mice were injected, inhaled and sprayed with OVA for 12 weeks (four a week) for asthma induction. Two experimental groups were treated with different concentrations of MGTG (400 mg/kg and 200 mg/kg) extract and cyclosporin A (10 mg/kg) for the later 8 weeks. At the end of the experiment, the mice lung was removed and analyzed CD3+ T cells, CD4+ T cells and CD8+ T cells by flow cytometer. Results: Numbers of CD3+ T cells in lung of the MGTG groups (200, 400 mg/kg) were significantly decreased compared with that of control group. Numbers of CD4+ T cells in lung of the MGTG groups (200, 400 mg/kg) were significantly decreased compared with that of control group. Numbers of CD8+ T cells in lung of the MGTG groups (200, 400 mg/kg) were significantly decreased compared with that of control group. Conclusion: The results of this study suggest that MGTG alleviated asthmatic hyperreactiviry through CD4+ and CD8+ T cells. Further study of relative cytokines is expected.