• IMMUNE NETWORK
• /
• 제21권2호
• /
• pp.17.1-17.10
• /
• 2021

Abdominal aortic aneurysm (AAA) is a chronic dilation of the aorta with a tendency to enlarge and eventually rupture, which constitutes a major cause of cardiovascular mortality. Although T-cell infiltrates have been observed in AAA, the cellular, phenotypic, and functional characteristics of these tissue-infiltrating T cells are not fully understood. Here, we investigated the proportional changes of T-cell subsets-including CD4⁺ T cells, CD8⁺ T cells, and γδ T cells-and their effector functions in AAAs. We found that Vδ2⁺ T cells were presented at a higher frequency in aortic aneurysmal tissue compared to normal aortic tissue and PBMCs from patients with AAA. In contrast, no differences were observed in the frequencies of CD4⁺, CD8⁺, and Vδ1⁺ T cells. Moreover, we observed that the Vδ2⁺ T cells from AAA tissue displayed immunophenotypes indicative of CCR5⁺ non-exhausted effector memory cells, with a decreased proportion of CD16⁺ cells. Finally, we found that these Vδ2⁺ T cells were the main source of IL-17A in abdominal aortic aneurysmal tissue. In conclusion, our results suggest that increased Vδ2⁺ T cells that robustly produce IL-17A in aortic aneurysmal tissue may contribute to AAA pathogenesis and progression.

• 미생물학회지
• /
• 제50권2호
• /
• pp.169-172
• /
• 2014

최근 인간 간암세포주(human hepatoma cells)를 이용하여 C형 간염 바이러스(hepatitis C virus, HCV)의 복제가 가능한 세포배양모델(cell culture system)이 확립되었다. 본 연구에서는 인간 간암세포주 중 huh7.5 cell (human hepatoma 7.5 cells)과 C형 간염 바이러스인 J6/JFH1 clone (2a 유전자형)를 이용하여 감염 가능한 세포배양모델을 확립하였다. 또한, HCV 감염 간암세포주의 HCV 특이 T 림프구에 대한 항원제시(antigen presentation) 가능성을 살펴보았다. 외부에서 전달된 HCV 항원일 경우 간암세포주의 HCV 특이 T 림프구에 대한 항원제시로 T 림프구의 활성이 가능하였으나, HCV 감염 간암세포주의 경우 T 림프구의 활성을 억제하였다. 이러한 HCV 특이 T 림프구의 활성억제와 HCV 감염 간암세포주 항원제시능의 상관성을 알아보기 위해 HCV 감염 간암세포주의 주조직적합성복합체(major histocompatibility complex, MHC) 발현변화를 측정하였으나 HCV 감염은 간암세포주의 MHC 발현변화에 영향을 미치지 않았다.

• Molecules and Cells
• /
• 제44권11호
• /
• pp.795-804
• /
• 2021

Memory T (T_M) cells play an important role in the long-term defense against pathogen reinvasion. However, it is still unclear how these cells receive the crucial signals necessary for their longevity and homeostatic turnover. To understand how T_M cells receive these signals, we infected mice with lymphocytic choriomeningitis virus (LCMV) and examined the expression sites of neural cadherin (N-cadherin) by immunofluorescence microscopy. We found that N-cadherin was expressed in the surroundings of the white pulps of the spleen and medulla of lymph nodes (LNs). Moreover, T_M cells expressing high levels of killer cell lectin-like receptor G1 (KLRG1), a ligand of N-cadherin, were co-localized with N-cadherin⁺ cells in the spleen but not in LNs. We then blocked N-cadherin in vivo to investigate whether it regulates the formation or function of T_M cells. The numbers of CD127^hiCD62L^hi T_M cells in the spleen of memory P14 chimeric mice declined when N-cadherin was blocked during the contraction phase, without functional impairment of these cells. In addition, when CD127^loKLRG1^hi T_M cells were adoptively transferred into anti-N-cadherin-treated mice compared with control mice, the number of these cells was reduced in the bone marrow and LNs, without functional loss. Taken together, our results suggest that N-cadherin participates in the development of CD127^hiCD62L^hi T_M cells and homing of CD127^loKLRG1^hi T_M cells to lymphoid organs.

• IMMUNE NETWORK
• /
• 제20권1호
• /
• pp.6.1-6.20
• /
• 2020

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

• Molecules and Cells
• /
• 제39권6호
• /
• pp.468-476
• /
• 2016

PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether $PLZF^+$ innate T cells also affect the development and function of $Foxp3^+$ regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant $PLZF^+$ CD4 T cells and invariant natural killer T cells, respectively, revealed that $Foxp3^+$ T cells in these mice exhibited a $CD103^+$ activated/memorylike phenotype. The frequency of $CD103^+$ regulatory T cells was considerably decreased in $PLZF^+$ cell-deficient $CIITA^{Tg}Plzf^{lu/lu}$ and $BALB/c.CD1d^{-/-}$ mice as well as in an IL-4-deficient background, such as in $CIITA^{Tg}IL-4^{-/-}$ and $BALB/c.IL-4^{-/-}$ mice, indicating that the acquisition of an activated/ memory-like phenotype was dependent on $PLZF^+$ innate T cells and IL-4. Using fetal thymic organ culture, we further demonstrated that IL-4 in concert with TGF-${\beta}$ enhanced the acquisition of the activated/memory-like phenotype of regulatory T cells. In functional aspects, the activated/ memory-like phenotype of Treg cells was directly related to their suppressive function; regulatory T cells of $CIITA^{Tg}PIV^{-/-}$ mice more efficiently suppressed ovalbumin-induced allergic airway inflammation compared with their counterparts from wild-type mice. All of these findings suggest that $PLZF^+$ innate T cells also augmented the generation of activated/memory-like regulation via IL-4 production.

• Journal of Microbiology and Biotechnology
• /
• 제14권5호
• /
• pp.891-900
• /
• 2004

UDP-N-Acetylglucosamine(GlcNAc):$\beta$1,4-D-mannoside$\beta$-l ,4N-acetylglucosaminyltransferase-III (GnT-III) and UDP-N-GlcNAc:$\alpha$-6-D-mannosid$\beta$-1,6N-acetylglucosaminyltransferase-V(GnT - V) activities were determined in human hepatoma cell lines and metastatic colon cancer cells, and their activities were compared with those of normal liver cells and fetal hepatocytes. GnT-III activities were higher than those of GnT-V in hepatic carcinoma cells. When the two enzyme activities were assayed in highly metastatic colon cancer cells, GnT - V activities were much higher than those of GnT-III. When GlcN, GlcN-biant-PA and UDP-GlcNAc were used as substrates, the enzymes displayed different kinetic properties between hepatic and colon cancer cells, depending on their metastatic potentials. Normal cells of two origins had characteristically very low levels of GnT-III and -V activities, whereas hepatoma and colon cancer cells contained high levels of activities. These data were supported by RT-PCR and Northern blot analyses, showing that the expression of GnT-III and -V mRNAs were increased in proportion to the enzymatic activities. The increased GnT-III, md -V activities were also correlated with increased glycosylation of the cellular glycoproteins in hepatoma and colon cancer cells, as examined by lectin blotting analysis by using wheat germ glutinin (WGA), erythroagglutinating phytohemagglutinin (E-PHA), leukoagglutinating phytohemagglutinin (L-PHA), and concanavalin A (Con A). Treatment with retinoic acid, a differentiation agent, resulted in decreases of both GnT-III and -V activities of HepG2 and HepG3 cells. In colon carcinoma cells, however, treatment with retinoic acid resulted in a reduction of GnT-V activity, but not with GnT-III activity. Although the mechanism underlying the induction of these mzymes is unclear, oligosaccharides in many glycoproteins have been observed of cancer cells.

• 생약학회지
• /
• 제29권2호
• /
• pp.110-119
• /
• 1998

Sa-Mul-Tang(SMT) consist of Rehmanniae Radix Preparata, Paeoniae Radix Alba, Cnidii Rhizoma and Angelicae Gigantis Radix. In L1210 cells-transplanted BALB/c mice, T-lymphocyte apoptosis, $CD8^+T_C$ cells population in thymocyte and nitric oxide production in macrophage were enhanced, but phagocytic activity was decreased. SMT suppressed T-lymphocyte apoptosis and enhanced CD^4+T_H$ cells population, but did not affect nitric oxide production and phagocytic activity in L1210 cells-transplanted mice. In antitumor drugs-injected mice, T-lymphocyte apoptosis was enhanced, but $CD4^+T_H/CD8^+T_C$, cells population and T-lymphocyte proliferation were decreased. SMT suppressed T-lymphocyte apoptosis, and enhanced $CD8^+T_C$ cells population, T-lymphocyte proliferation and phagocytic activity in vincristine-injected mice. These results suggest that SMT enhances T cell-mediated immunity in L1210 cell-transplanted mice, and enhances T cell-mediated immunity and phagocytic activity in vincristine-injected mice.

• Biomolecules & Therapeutics
• /
• 제24권3호
• /
• pp.244-251
• /
• 2016

Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of $TGF-{\beta}$. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Cotransfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.

• Molecules and Cells
• /
• 제25권1호
• /
• pp.64-69
• /
• 2008

Although the arthritis symptoms observed in the K/BxN model have been shown to be dependent on the functions of T and B cells specific to the self antigen glucose-6-phosphate isomerase, less is known about the in vivo roles of $CD4^{+}CD25^{+}$ regulatory T($T_{reg}$) cells in the pathology of K/BxN mice. We determined the quantitative and functional characteristics of the $T_{reg}$ cells in K/BxN mice. These mice contained a higher percentage of $Foxp3^+\;T_{reg}$ cells among the $CD4^+$ T cells than their BxN littermates. These $T_{reg}$ cells were anergic and efficiently suppressed the proliferation of $na\ddot{i}ve$ $CD4^+$ T cells and cytokine production by effector $CD4^+$ T cells in vitro. Antibody-mediated depletion of $CD25^+$ cells caused K/BxN mice to develop multi-organ inflammation and autoantibody production, while the symptoms of arthritis were not affected. These results demonstrate that despite the inability of the $T_{reg}$ cells to suppress arthritis development, they play a critical role protecting the arthritic mice from systemic expansion of autoimmunity.

• 대한한의학회지
• /
• 제28권2호통권70호
• /
• pp.126-136
• /
• 2007

Objectives : In the present study, the effect of Kuwonsimsin-hwan (KSS) was tested in methotrexate (MTX)-induced immunosuppressed SD rats. Methods : Methotrexate was fed to white rats once a day for 4 days. After the immune responses of the rats deteriorated, dried extracts of Kuwonsimsin-hwan mixed in water was fed to the rats once a day for 14 days. We then measured the number of lymphocytes in peripheral blood and the percentage of B-cells, T-cells, CD3+CD4+T-cells, CD3+CD8+ T-cells and IL-2 productivity sampled from spleen and peripheral region. Results : (1) The number of lymphocytes and the percentage of T-cells and CD3+CD4+ T-cellsin peripheral blood increased significantly in the KSS group as compared with the control group. (2) The percentage of B-cells, CD3+CD8+ T-cells, and CD4+/CD8+ T-cells in peripheral blood were not different statistically. (3) The percentage of T-cells in spleen and IL-2 productivity of spleen cells increased significantly in the KSS group as compared with the control group. (4) The percentage of CD3+CD4+ T-cells in spleen increased in KSS the group as compared with the control group but without statistical significance. (5) The percentage of B-cells, CD3+CD8+ T-cells, and CD4+/CD8+ T-cells in spleen were not different statistically. Conclusion : It is concluded that Kuwonsimsin-hwan has immunostimulating effect on MTX-induced immunosuppressed SD rats.