• IMMUNE NETWORK
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• 제5권1호
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• pp.23-29
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• 2005

Background: Interleukin-7 receptor (IL-7R) ${\alpha}$-deficient mice have small numbers of B cells and ${\alpha}{\beta}$T cells in periphery, they totally lack ${\gamma}{\delta}$T cells. In addition, the V-J recombination and transcription of TCR ${\gamma}$ genes is also severely impaired in IL-7R ${\alpha}$-deficient mice. Stat5, a signaling molecule of the IL-7R, induces germline transcription in the TCR ${\gamma}$ locus, and promotes V-J recombination and ${\gamma}{\delta}$T cell development. However, the roles for IL-7R signaling pathway in thymic or extrathymic ${\gamma}{\delta}$T cell development are largely unknown. Methods: To clarify the role of the IL-7 receptor in proliferation and survival of ${\gamma}{\delta}$T cells, we introduced the TCR ${\gamma}{\delta}$ transgene, $V_{{\gamma}2}/V{\delta}_5$, into IL-7R ${\alpha}$-deficient mice, and investigated the development of ${\gamma}{\delta}$T cells. Results: We found that $V_{{\gamma}2}/V{\delta}_5$ transgene restored ${\gamma}{\delta}$T cells in the epithelium of the small intestine (IEL) but not in the thymus and the spleen. Further addition of a bcl-2 transgene resulted in partial recovery of ${\gamma}{\delta}$T cells in the thymus and the spleen of these mice. Conclusion: Taken together, this study revealed that the IL-7R ${\alpha}$ is indispensable for proliferation and survival mainly in thymic ${\gamma}{\delta}$T cell development.

• Parasites, Hosts and Diseases
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• 제40권3호
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• pp.119-129
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• 2002

Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.

• Tuberculosis and Respiratory Diseases
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• 제41권5호
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• pp.484-488
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• 1994

연구배경 : 최근에 ${\gamma}{\delta}$ T 램프구가 결핵균의 항원과 반응함이 알려져 ${\gamma}{\delta}$ T 림프구가 결핵균에 대한 방어기전에 관여할 가능성이 제시되고 있다. 본 교실의 연구와 다른 연구에 의하면 폐결핵 환자의 말초혈액에서 ${\gamma}{\delta}$ T 림프구의 숫적 증가나 기능의 활성화가 관찰되지 않아 폐결핵 환자에서 ${\gamma}{\delta}$ T 림프구는 전신적으로 활성화되지 않고 국소병변에서 방어기능을 나타내는 것으로 생각할 수 있다. 이에 저자들은 일차적으로 결핵의 국소병변으로 조직을 얻기가 쉬운 결핵성 림프절에서 ${\gamma}{\delta}$ T 림프구의 분포를 관찰하고자 본 연구를 시행하였다. 방법 : 조직검사상 결핵성 림프절염(n=5)과 반응성 과형성(reactive hyperplasia) (n=3)으로 진단된 환자의 림프절을 대상으로 CD4, ${\alpha}{\beta}$ TCR, ${\gamma}{\delta}$ TCR에 대한 단일 클론항체를 이용해 면역조직화학검사를 시행하였다. 결과 : 반응성 과형성 림프절에서는 총 T 림프구중 ${\gamma}{\delta}$ T 림프구의 비율이 $1.7{\pm}1.5%$였고 결핵성 림프절에서는 ${\gamma}{\delta}$ T 림프구가 전체 T 림프구의 $16.3{\pm}10.3%$를 차지하고 있어 결핵성 림프절에서 반응성 과형성 림프절에 비해 ${\gamma}{\delta}$ T 림프구의 침윤이 유의하게 증가되어 있었다(p<0.05). 결론 : ${\gamma}{\delta}$ T 림프구가 결핵균 감염 국소 병변부위에서 방어기전에 관여할 가능성이 있을 것으로 생각되고 향후 국소 결핵 병변에서의 ${\gamma}{\delta}$ T 림프구 기능에 관한 연구가 필요할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제41권3호
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• pp.239-247
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• 1994

연구배경: ${\gamma}{\delta}$ T 림프구가 새로 발견된 이후 아직 명확한 기능이 밝혀지지 않았지만 M.tuberculosis의 HSP65에 반응함이 보고되었다. 아직도 결핵의 유병률이 높은 현실을 감안하여 폐결핵환자를 대상으로 하여 본 연구를 시행하였다. 방법: 16예의 건강대조군과 22예의 폐결핵군에서 말초혈액을 채취하여 PPD, Con-A, 그리고 H37Ra lysate로 자극하였으며, 자극전후의 ${\gamma}{\delta}$ T 림프구의 비율과 활성도를 유세포계측을 이용하여 측정하였다. 결과: 1) 건강대조군의 말초혈액의 총 T 림프구 중에서 ${\gamma}{\delta}$ T 림프구의 비율은 $10.0{\pm}4.8%$ 이었고, 폐결핵군에서는 $7.5{\pm}5.2%$로 통계적으로 유의한 차이는 없었다. 2) PPD, Con-A, 그리고 H37Ra lysate로 자극한 후에도 ${\gamma}{\delta}$ T 림프구의 비율은 유의한 변화가 없었다. 3) ${\gamma}{\delta}$ T 림프구 중에서 IL-2R(+)인 비율은 건강대조군에서 $1.8{\pm}2.8%$, 그리고 폐결핵군에서는 4.8%로 폐결핵군에서 유의하게 높았다. 4) PPD 또는 Con-A로 자극후 양군 모두에서 IL-2R(+)의 비율은 통계적으로 유의하게 증가되었다. 5) PPD 피부반응검사와 말초혈액의 ${\gamma}{\delta}$ T 림프구의 비율간에는 유의한 상관관계가 없었다. 결론: 본 연구에서는 폐결핵환자의 말초혈액에서 ${\gamma}{\delta}$ T 림프구의 역할을 규명할 수 없었다. 국소병변에서의 ${\gamma}{\delta}$ T 림프구에 대한 연구가 더 필요하리라 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제44권1호
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• pp.44-51
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• 1997

연구배경 : 최근 알려진 ${\gamma}{\delta}$ 수용체는 결핵균 감염의 초기에 제2형 주요 조직적합성 복합계(MHC class II)의 인식없이 결핵균 항원에 반응하여 세포성 면역반응을 나타냄이 보고되었다. 이에 연구자등은 페결핵환자와 결핵성 흉막염 환자, 그리고 다른 원인의 흉막염 환자사이에 T 림프구의 조성과 ${\gamma}{\delta}$ T-림프구 수의 차이를 관찰하였다. 방법 : 대상은 폐결핵환자 30예(이중 결핵성 흉막염환자 15예), 폐암 환자 12예(이중 악성 흉막염 환자 9예), 폐렴 7예(이중 폐렴성 흉막염 6예)등 모두 49예였다. 혈청 ADA(adenosine deaminase)활성도는 Hitachi 747 자동화학분석기에서 측정하였다. T 세포 림프구 아형의 분류는 lysed whole blood method로 anti-Leu4, anti-Leu3a, anti-Leu2a, anti HLA-DR 그리고 anti-TCR-${\gamma}{\delta}$-1를 이용하여 flow cytometer로 분석하였다. 결과 : 1. 말초혈액내 ${\gamma}{\delta}$-T 림프구의 평균치는 $4.8{\pm}4.6%$ 였고, 결핵군(29예) $5.5{\pm}4.5%$, 비결핵군(14예) $3.3{\pm}2.9%$(폐암군 $4.0{\pm}3.2%$, 폐렴군 $2.2{\pm}1.6%$로 유의한 차이는 없었다(p=0.24). 질병의 이환기간 1개월 이내의 환자중에서도 결핵군(20예) $6.4{\pm}6.6%$, 비결핵군(14예) $3.3{\pm}2.9%$ 으로 유의한 차이는 없었다(p=0.16)(Table 1). 2. 흉막액내 T 세포 림프구 아형중 CD4 림프구는 결핵성 흉막액에서는 $54.6{\pm}13.8%$, 비결핵성 흉막액에서는 $36.2{\pm}25.3%$(악성 흉막액 $38.4{\pm}23.8%$, 폐렴정 흉막액 $30.1{\pm}34.0%$ 결핵성 흉막액에서 의의있게 높았다(p=0.04)(Table 2). 3. 흉막염이 있던 환자에서 말초혈액내 ${\gamma}{\delta}$-T 림프구는 결핵성 흉막염군(14예)이 $7.0{\pm}9.0%$, 비결핵성 흉막염군(11예) $3.0{\pm}2.0%$ (악성 흉막염군 $3.1{\pm}2.2%$, 폐렴성 흉막염군 $2.7{\pm}1.7%$로 차이는 없었다(p=0.16). 흉막액내 ${\gamma}{\delta}$-T 림프구는 결핵성 흉막염군(15예)이 $3.9{\pm}2.9%$, 비결핵성 흉막염군(10예) $2.1{\pm}2.2%$(악성 흉막염군 $2.0{\pm}2.5%$, 폐렴성 흉막염군 $2.4{\pm}1.7%$ 로 유의한 차이가 없었다(p=0.12). 4. 환자의 연령이나 성별과 말초혈액내 ${\gamma}{\delta}$-T 림프구수와는 상관관계가 없었고, 폐결핵 환자에서 병변의 정도, 혈청 및 흉막액내 ADA와 ${\gamma}{\delta}$-T 림프구수와도 상관관계가 없었다. 결론 : 결핵성 흉막염환자에서 말초혈액 및 흉막액내 ${\gamma}{\delta}$-T 림프구수의 유의한 증가는 없어 다른 질환과의 감별진단에 도움이 되지 못할 것으로 생각되며, ${\gamma}{\delta}$-T 림프구의 증가는 결핵 초기 환자들을 대상으로 추가 연구가 필요할 것으로 생각된다.

• 대한본초학회지
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• 제21권1호
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• pp.51-56
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• 2006

Objectives : To clarify the effects of Actinidia polygama and CsA on OVA-induced asthma model, we examined the influence of Actinidia polygama fructus extract (APF) and CsA on the number of regulatory T cells, NKT cells and ${\gamma}{\delta}$ T cells in murine model of asthma. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by i.p. injections of OVA in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 min/day on 3 days/week for 12 weeks and APF (400, 40 mg/kg) were orally administered 3 times a week for 8 weeks. Results : The suppressive effects of APF on asthma model were demonstrated by the increase the number of regulatory T cells, ${\gamma}{\delta}$ T cells and by reducing the number of NK T cells. Conclusion : These results indicate that APF has a deep inhibitory effect on airway inflammation and hyperresponsiveness in murine model of asthma by increase the number of regulatory T cells, and ${\gamma}{\delta}$ T cells and by reducing the number of NK T cells.

• IMMUNE NETWORK
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• 제15권3호
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• pp.142-149
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• 2015

Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPNdeficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and IL-17-producing ${\gamma}{\delta}$ T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and the percentage of IFN-$\gamma$-producing ${\gamma}{\delta}$ T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in $CD4^+$ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-$\gamma$ T cells.

• Fisheries and Aquatic Sciences
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• 제8권2호
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• pp.56-64
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• 2005

Two distinct CD3 homologue genes, $CD3\gamma/\delta\;and\;CD\varepsilon$, were isolated from a olive flounder leukocyte cDNA library and a BAC library. $CD3\gamma/\delta$ consisted of 961 bp encoding 178 amino acid residues, and $CD3\varepsilon$ consisted of 1006 bp encoding 164 amino acid residues. When compared with other known CD3 peptide sequences, the most conserved region of the two olive flounder CD3 chain peptides are the cytoplasmic domain and the least conserved are the extracellular domain. A phylogenetic analysis based on the deduced amino acid sequence grouped the two olive flounder CD3 sequences with $CD3\varepsilon$ and $CD3\gamma/\delta$, respectively. The olive flounder CD3 cluster (consisting of $CD3\varepsilon\;and\;CD3\gamma/\delta$) spans only 10.4 kb. The $CD3\varepsilon\;and\;CD3\gamma/\delta$ genes are oppositely transcribed only 3.8 kb apart. Both olive flounder CD3 genes have five exons. The two olive flounder CD3 genes were predominantly expressed in PBLs, kidney, spleen, and gills.

• IMMUNE NETWORK
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• 제20권1호
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• pp.5.1-5.15
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• 2020

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

• IMMUNE NETWORK
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• 제11권6호
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• pp.406-411
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• 2011

Background: Invariant Natural killer T (iNKT) cells, a distinct subset of CD1d-restricted T cells with invariant $V{\alpha}{\beta}$ TCR, functionally bridge innate and adaptive immunity. While iNKT cells share features with conventional T cells in some functional aspects, they simultaneously produce large amount of Th1 and Th2 cytokines upon T-cell receptor (TCR) ligation. However, gene expression pattern in two types of cells has not been well characterized. Methods: we performed comparative microarray analyses of gene expression in murine iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells by using Gene Set Enrichment Analysis (GSEA) method. Results: Here, we describe profound differences in gene expression pattern between iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells. Conclusion: Our results provide new insights into the functional competence of iNKT cells and a better understanding of their various roles during immune responses.