• IMMUNE NETWORK
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• 제6권2호
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• pp.93-101
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• 2006

Background: Memory T lymphocytes of the immune system provide long-term protection in response to bacterial or viral infections/immunization. Ag concentration has also been postulated to be important in determining whether T cell differentiation favors effector versus memory cell development. In the present study we hypothesized that naive Ag-specific $CD4^+$ T cells briefly stimulated with different Ag doses at the primary exposure could affect establishment of memory cell pool after secondary immunization. Methods: To assess this hypothesis, the response kinetics of DO11.10 TCR $CD4^+$ T cells primed with different Ag doses in vitro was measured after adoptive transfer to naive BALB/c mice. Results: Maximum expansion was shown in cells primarily stimulated with high doses of ovalbumin peptide $(OVA_{323-339})$, whereas cells in vitro stimulated with low dose were expanded slightly after in vivo secondary exposure. However, the cells primed with low $OVA_{323-339}$ peptide dose showed least contraction and established higher number of memory cells than other treated groups. When the cell division was analyzed after adoptive transfer, the high dose Ag-stimulated donor cells have undergone seven rounds of cell division at 3 days post-adoptive transfer. However, there was very few division in naive and low dose of peptide-treated group. Conclusion: These results suggest that primary stimulation with a low dose of Ag leads to better memory $CD4^+$ T cell generation after secondary immunization. Therefore, these facts imply that optimally primed $CD4^+$ T cells is necessary to support effective memory pool following administration of booster dose in prime-boost vaccination.

• Journal of Microbiology and Biotechnology
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• 제30권3호
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• pp.439-447
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• 2020

We investigated the immune restoration activity of Undaria pinnatifida fucoidan-rich extract in cyclophosphamide-induced immunosuppressed mice. C57BL/6 mice were intraperitoneally injected with 80 mg/kg of cyclophosphamide (CP) and orally administered with either drinking water (DW), red ginseng extract (RG), or one of three different doses of Undaria pinnatifida fucoidan-rich extract (DSU02 50, 100, and 150 mg/kg). After 14 days, liver, spleen, and whole blood were isolated from each animal. The frequencies of NK and CD³⁺, CD⁴⁺, and CD⁸⁺ T cells were significantly increased in splenocytes isolated from the DSU02 100 mg/kg and DSU02 150 mg/kg groups (NK1.1+, 5.4% or 4.9% vs 3.8%; CD³⁺, 39.3% or 37.9% vs 32.3%; CD4+, 22% or 20.2% vs 17.4%; CD8+, 12.7% or 11.6% vs 10.1%). NK cytotoxicity was enhanced in the DSU02-fed groups at all doses (CP-treated DW, 93.4%; RG, 107.2%; DSU02 50, 107.3%; DSU02 100, 107.3%; DSU02 150, 107.1%), and the proliferation of T cells (CD³⁺, CD⁴⁺, and CD⁸⁺) was also greater in the DSU02 100 mg/kg and DSU02 150 mg/kg administered groups compared with the unfed group. Plasma concentrations of TNF-α, IgM, and total IgG from the DSU02 150 mg/kg group were also significantly higher compared with the other groups (TNF-α: CP-treated DW - 21.5 pg/ml, DSU02 150 - 47.1 pg/ml; IgM: CP-treated DW - 82.9 ng/ml, DSU02 150 - 110.8 ng/ml; total IgG: CP-treated DW - 114.4 ng/ml, DSU02 150 - 162.7 ng/ml). We suggest that Undaria pinnatifida fucoidan-rich extract could be a promising candidate for a marine natural immune stimulator.

• IMMUNE NETWORK
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• 제5권4호
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• pp.221-231
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• 2005

Background: Immune regulatory dendritic cells (DCs) play an important role in maintaining self-tolerance. Recent evidences demonstrate that DCs expressing indoleamine 2,3-dioxygenase (IDO), which is involved in tryptophan catabolism, play an important role in immunoregulation and tolerance and induce T cell apoptosis. This study was devised to examine the role of IDO in the oral tolerance induction in collagen-induced arthritis (CIA) mouse model. Methods: Beginning 2 weeks before immunization, CII was fed six times to DBA/1 mice and the effect on arthritis was assessed. In tolerized mice, $CD11c^+$ DCs were isolated and stimulated with CII, IFN-${\gamma}$, and LPS with or without IDO inhibitor, 1-methyl-DL-tryptophan (1-MT) and IDO expression by $CD11c^+$ DCs was analyzed using FACS and RT-PCR. The expression of IDO, MHC II, CD80, and CD86 by $CD11c^+$ DCs were examined using confocal microscopy. Regulatory effect of $CD11c^+$ DCs on Ag-specific T cell proliferative response to CII was examined by mixed lymphocyte reaction (MLR) with or without 1-MT. Results: The proportion of IDO-expressing $CD11c^+$ DCs was slightly higher in tolerized mice than in CIA mice and significantly increased after stimulation with CII, IFN-${\gamma}$, and LPS in an IDO-dependent manner. On confocal microscopic examination, the expression of IDO was higher and those of MHC II and CD86 were lower in CD11c + DCs from tolerized mice compared to those from CIA mice. On MLR, $CD11c^+$ DCs from tolerized mice inhibited T cell proliferative response to CII in an IDO-dependent manner. Conclusion: Enhanced IDO expression by $CD11c^+$ DCs from tolerized mice may contribute to the regulation of proliferative response of CII-reactive T cells and could be involved in the induction of oral tolerance to CII.

• Journal of Ginseng Research
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• 제48권1호
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• pp.68-76
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• 2024

Background: Although the survival outcomes of childhood cancer patients have improved, childhood cancer survivors suffer from various degrees of immune dysfunction or delayed immune reconstitution. This study aimed to investigate the effect of Korean Red Ginseng (KRG) on T cell recovery in childhood cancer patients who underwent autologous hematopoietic stem cell transplantation (ASCT) from the perspective of inflammatory and senescent phenotypes. Methods: This was a single-arm exploratory trial. The KRG group (n = 15) received KRG powder from month 1 to month 12 post-ASCT. We compared the results of the KRG group with those of the control group (n = 23). The proportions of T cell populations, senescent phenotypes, and cytokine production profiles were analyzed at 1, 3, 6, and 12 months post-ASCT using peripheral blood samples. Results: All patients in the KRG group completed the treatment without any safety issues and showed a comparable T cell repopulation pattern to that in the control group. In particular, KRG administration influenced the repopulation of CD4⁺ T cells via T cell expansion and differentiation into effector memory cell re-expressing CD45RA (EMRA) cells. Although the KRG group showed an increase in the number of CD4⁺ EMRA cells, the expression of senescent and exhausted markers in these cells decreased, and the capacity for senescence-related cytokine production in the senescent CD28^- subset was ameliorated. Conclusions: These findings suggest that KRG promotes the repopulation of CD4⁺ EMRA T cells and regulates phenotypical and functional senescent changes after ASCT in pediatric patients with cancer.

• 한국식품영양과학회지
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• 제45권11호
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• pp.1564-1570
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• 2016

본 연구에서는 고순도 ${\beta}$-1.3/1.6-glucan이 선천면역계에 중요한 역할을 하는 대식세포와 자연살해세포의 활성화와 적응면역계에서 중요한 역할을 하는 T 세포 면역계에 대한 면역조절 효과를 살펴보고자 대식세포의 활성능, 자연살해 세포의 활성능, 그리고 T 세포 면역계에 조절작용을 하는 사이토카인, CD4+/CD8+ T 세포에 미치는 영향을 관찰하였다. 마우스 복강에서 불리한 대식세포를 이용하여 세포독성을 확인한 결과 고순도 ${\beta}$-1.3/1.6-glucan $10{\sim}200{\mu}g/mL$의 농도에서 독성이 나타나지 않았다. 또한, 고순도 ${\beta}$-1.3/1.6-glucan은 대식세포의 활성능, 자연살해세포의 활성능에 도움을 주어 활성능을 증가시켜 외부로부터 침입한 미생물, 감염된 세포나 종양세포 등을 효과적으로 제거할 수 있을 것이라 예상할 수 있었다. 마지막으로 T 세포 면역계에 조절작용을 하는 사이토카인과 CD4+/CD8+를 확인한 결과 고순도 ${\beta}$-1.3/1.6-glucan이 사이토카인들의 분비량 및 CD4+/CD8+를 증가시켜 T 세포 면역계에 조절뿐아니라 B 세포 면역계의 조절에 도움을 줄 것이라 예상할 수 있었다. 결론적으로 고순도 ${\beta}$-1.3/1.6-glucan은 선천면역뿐 아니라 적응면역에서 영향을 미칠 것이라 생각하며 면역조절에 긍정적인 변화를 보였으므로 추후 면역 조절제로서 기능성 식품의 상업화에 기초 자료가 되어 국내 기능성 소재로서의 개발 가능성을 기대할 수 있다.

• Journal of Ginseng Research
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• 제45권5호
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• pp.591-598
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• 2021

Background: Hematopoiesis is the production of blood cells from hematopoietic stem cells (HSCs) that reside in the bone marrow. Cyclophosphamide (CTX) is a chemotherapy drug that suppresses the immune system. Korean Red Ginseng (KRG) and Colla corii asini (CCA) have been traditionally used for boosting the immune system. Methods: HSCs in the bone marrow, and immune cell subtype in splenocytes, PBMCs, and thymocytes were investigated. Serum levels of hematopoietic-related markers were analyzed using ELISA. Protein expression in spleen tissue was analyzed using western blot analysis. Hematoxylin & eosin staining in the femurs of mice were also conducted. Results: The combination of KRG and CCA with a ratio of 3:2 increased HSCs, CD3 and CD8⁺ T cells in the circulation, and CD3 T cells in the spleen. A ratio of 2:3 (KRG:CCA) increased the thymic regulatory T cells and recovered the CD3 T cells in the spleen and circulation while recovering proteins in the JAK-STAT pathway in the spleen. Overall, blood cell population and differentiating factors vital for cell differentiation were also significantly recovered by all combinations especially in ratios of 3:2 and 2:3. Conclusion: A ratio of 3:2 (KRG:CCA) is the most ideal combination as it recovered the HSC population in the bone marrow of mice.

• Natural Product Sciences
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• 제17권4호
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• pp.354-362
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• 2011

Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by abnormalities in T cell immunoregulation and hyperreactivity of B cells, leading to autoantibody production and multiorgan injuries. We investigated the effect of baicalin on aberrant immunoregulation in pristane-induced lupus mice. Mice received i.p. a single injection of 0.5 ml of pristane or PBS, and approximately 3 months later, were used as a pristane-induced lupus model or healthy controls. The pristane-induced lupus mice and healthy mice were randomly divided into three groups: healthy mouse group (healthy control), pristane-primed lupus control group (lupus control), and baicalin (BAC)-treated pristane-primed lupus mouse group (BAC-treated lupus). The pristane-induced lupus mice and healthy mice were administrated orally with BAC 50 mg/kg or PBS once in a day for 10 ds. These results demonstrated that levels of serum IL-6, LPS-induced production of IL-6, $PGE_2$ and NO by macrophages, $PGE_2$-stimulated production of IL-6 by macrophages and IFN-${\gamma}$ by thymocytes, and an overexpression of splenic NKT cells and CD69+CD4+ T cells were downregulated in BAC-treated lupus compared to lupus control, while reduced apoptosis of splenic CD4+ T cells were upregulated. Therefore, these findings suggest that BAC may attenuate autoimmunity and disease activity in lupus via downregulation of aberrant activation of T cells and inhibition of overproduction of IL-6 and $PGE_2$ in pristane-induced lupus mice.

• 대한수의학회지
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• 제41권3호
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• pp.373-380
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• 2001

Marek's disease virus (MDV) can cause skin lesions including inflammatory to tumorous. The phenotypical changes of lymphocytes infiltrating in the skin lesions induced by MDV were not clear. Therefore, the skin biopsies taken at weekly intervals for 8 weeks from the same specific-pathogen free chickens inoculated with Md/5 MDV were examined to analysis the phenotypical changes of lymphocytes. Histologically skin lesions progressed from initial inflammatory to late tumorous. Sequentially CD4+ T lymphocytes increased gradually in number from initial skin lesions and were major composition cells in the tumor lesions. Regardless of inflammatory or tumor lesions, CD8+ T cells and ${\gamma}{\delta}$ T cells infiltrated particularly in the dermis and subcutaneous on which MDV was actively replicated in the feather follicle epithelium(FFE). In addition, IgG bearing B lymphocytes in considerable number infiltrated in the dermis and subcutaneous tissues. From these results, the development of MDV-induced skin lesions was inflammatory following tumorous. In addition, each CD8+, ${\gamma}{\delta}$ and CD4+ T cells and B cell might act to protect MDV replication in the FFE or tumor cells which turned on lytic cycle.

• Journal of Microbiology
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• 제39권3호
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• pp.181-185
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• 2001

The morphological characteristics of newly isolated Cordyceps hepialidicola were characterized, and the phylogenetic relationships with other Cordyceps species were investigated using a sequence analysis of the internal transcribed spacer (ITS). The PCR product of 592 bp showed a homology of 92 and 91% with C. militaris and C. nutans, respectively, In an in vitro model using mouse peripheral blood mononuclear cells (PBMC), a methanol extract of C. hepialidicola induced multiple cytokines, including IFN-${\gamma}$ IL-4, and IL-18. The extract also enhanced the percentages of the CD4$\^$+/ and CD8$\sub$+/ T cells in the healthy murine PBMCs to 56.1% and 13.0%,respectively. The percentages of CD4$\^$+/ and CD8$\^$+/ in the untreated controls were 28.4 and 7.3%, and concanavalin A-treated positive controls were 62.4 and 18.3%, respectively.

• IMMUNE NETWORK
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• 제20권5호
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• pp.38.1-38.12
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• 2020

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3⁺ induced Treg (iTreg) differentiation in ovalbumin-specific CD4⁺ T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.