• IMMUNE NETWORK
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• v.23 no.6
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• pp.44.1-44.16
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• 2023

Mesenchymal stem cells (MSCs) are effective in treating autoimmune diseases and managing various conditions, such as engraftment of allogeneic islets. Additionally, autologous and HLA-matched allogeneic MSCs can aid in the engraftment of human allogeneic kidneys with or without low doses of tacrolimus, respectively. However, HLA alloantigens are problematic because cell therapy uses more HLA-mismatched allogeneic cells than autologous for convenience and standardization. In particular, HLA-mismatched MSCs showed increased Ag-specific T/B cells and reduced viability faster than HLA-matched MSCs. In CRISPR/Cas9-based cell therapy, Cas9 induce T cell activation in the recipient's immune system. Interestingly, despite their immunogenicity being limited to the cells with foreign Ags, the accumulation of HLA alloantigen-sensitized T/B cells may lead to allograft rejection, suggesting that alloantigens may have a greater scope of adverse effects than foreign Ags. To avoid alloantigen recognition, the β2-microglobulin knockout (B2MKO) system, eliminating class-I MHC, was able to avoid rejection by alloreactive CD8 T cells compared to controls. Moreover, universal donor cells in which both B2M and Class II MHC transactivator (CIITA) were knocked out was more effective in avoiding immune rejection than single KO. However, B2MKO and CIITA KO system remain to be controlled and validated for adverse effects such as the development of tumorigenicity due to deficient Ag recognition by CD8 T and CD4 T cells, respectively. Overall, better HLA-matching or depletion of HLA alloantigens prior to cell therapy can reduce repetitive transplantation through the long-term survival of allogeneic cell therapy, which may be especially important for patients seeking allogeneic transplantation.

• Journal of Chest Surgery
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• v.31 no.12
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• pp.1119-1126
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• 1998

Background: In this study, we investigated the early time course of expression of the major histocompatibility(MHC) antigens, intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), interleukin-6 and the histopathological changes in the coronary arteries of cardiac allografts exchanged between inbred mice strains that differ in one loci of class I major histocompatibility antigen (B10.BR to B10.A). Material and Method: No immunosuppressive therapy was used. Both allografts and the hearts of the recipients were harvested at 7(group 1, n=6), 15(group 2, n=6), 21(group 3, n=6), and 30(group 4, n=6) days after transplantation. They were examined by immunohistochemistry, microscopy and morphometry. All allografts had contractions at the time of harvest. Result: A strong MHC class I antigen expression was present on the endothelial and medial cells of the coronary arteries in group 1 and remained unchanged in the rest of the groups. However, MHC class II reactivity was none or very little at any time. Mild to moderate ICAM-1 expression was observed on the endothelial cells, but not on the medial cells at any time by 30 days. VCAM-1 expression was strong both on the endothelial and medial cells at any time. Moderate degree expression of interleukin-6 was observed from 7 to 30 day specimens. Histopathologically, percentage of affected vessels(vessels with intimal thickening) was less than 10 % in 7 day group and increased up to 50 % at 30 days. Mean percent narrowing of the lumen of the affected vessels revealed less than 20 % at 7 days and 40 % at 30 days. The area occupied by tropomyosin positive cells in the intimal lesion, graded from 0 to 3, showed gradual increase but remained between grade 0 to 1 by 30 days. Medial integrity was also well preserved at any time. Moderate perivascular mononuclear cell infiltration was observed at 7 days and it was progressively increased upto 30 days. Recipients' heart revealed no positive immunopathologic findings. Conclusion: In this study, the early time course of progression of the transplantation vasculopathy was demonstrated in the murine heterotopic heart transplant model.

• IMMUNE NETWORK
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• v.22 no.3
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• pp.28.1-28.11
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• 2022

The 26S proteasome irreversibly hydrolyzes polyubiquitylated substrates to maintain protein homeostasis; it also regulates immune responses by generating antigenic peptides. An alternative form of the 26S proteasome is the immunoproteasome, which contains substituted catalytic subunits (β1i/PSMB9, β2i/PSMB10, and β5i/PSMB8) instead of constitutively expressed counterparts (β1/PSMB6, β2/PSMB7, and β5/PSMB5). The immunoproteasome expands the peptide repertoire presented on MHC class I molecules. However, how its activity changes in this context is largely elusive, possibly due to the lack of a standardized methodology to evaluate its specific activity. Here, we describe an assay protocol that measures the immunoproteasome activity of whole-cell lysates using commercially available fluorogenic peptide substrates. Our results showed that the most accurate assessment of immunoproteasome activity could be achieved by combining β5i-targeting substrate Ac-ANW-AMC and immunoproteasome inhibitor ONX-0914. This simple and reliable protocol may contribute to future studies of immunoproteasomes and their pathophysiological roles during viral infection, inflammation, and tumorigenesis.

• Journal of the korean veterinary medical association
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• v.25 no.10
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• pp.595-606
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• 1989

항원제시세포(APC)와 보조T세포 간의 협력작용에 의하여 활성화된 작동세포(NK세포, CTL, K세포, 대식세포, 과립구 등)의 종양세포, 이식장기 및 세포내기생세균에 감염된 각종 세포에 대한 세포독성작용은 생체방어를 위한 중요한 세포성면역기전이다. 지난 몇 년간 세포성면역기전에 관한 많은 연구에도 불구하고 T림파구매개성 세포독성작용의 면역생물학적기전은 확실히 밝혀있지 않다. 지금까지 알려진 중요한 연구내용을 요약하면 다음과 같다. 1. 세포독성작용을 나타내는 작동세포로는 NK세포, CTL, K세포, 대식세포/단핵구 및 과립구가 있다. 2. T세포의 세포표면항원분자군(CD)으로는 $CD_{2},\;CD_{3},\;CD_{4}[Ly_{3}T_{4}],\;CD_{5}[=Ly_{1}],\;CD_{7},\;CD_{8}[Ly_{2,3}]$가 있으며 $CD_{4}$는 보조Ttpvhdml 특이마커이고 $CD_{8}$는 세포독성 T세포 및 억압T세포의 특이마커이다. 주요 T세포수용체(TCR)는 $CD_{4}$ 또는 $CD_{8}$ 분자와 가까이 연합된 이향체($TCR-{\alpha}{\beta}/TCR-{\gamma}{\delta}$이며 보조 T세포 $CD_{4}$(마우스 $L_{3}T_{4}$)는 수용체와 연합되어 있는반면 억압 T세포 $CD_{8}(Ly+_{2,3})$는 항원수용체와 연합되어 있다. 3. T세포는 Ti-$CD_{3}$(항원/MHC) 복합체를 통한 '항원가교'에 의한 자극(항원인식)과 $CD_{2}$를 통한 비특이경로에 의하여 활성화(분화증식)된다. 비특이경로를 통한 활성경로에서 T세포($CD_{4}$ 및 $CD_{8}$)가 활성화되기 위하여는 보조T세포가 생산하는 IL-2을 요구하며 IL-2의 자극으로 분화증식된 $CD_{8}$는 세포독성능을 나타내지만 $CD_{4}^{+}$는 여전히 세포독성능을 나타내지 못한다. 4. 보조T세포는 class II MHC분자와 연합된 항원을 식별하는 반면 세포독성T세포는 class I MHC 분자와 연합된 항원을 식별한다. 5. 림파구 매개성 세포독성은 접촉(conjugati-on), 탈분극(depolarization), 용해계획(progra-mming), 용해(lysis) 및 재순환(recycling)의 단계를 거쳐 진행된다. 6. 표적세포살해매체로는 perforin / PFP / cy-tolysin, lymphopores, lymphotoxins, protone, cytolytic enzymes가 알려졌으며 세포독성작용은 이들 이외에도 여러 가지 매체를 통한 복합작용으로 추정된다. 7. CTL 매개성 표적세포의 주요 대사변화는 actomyocin ATPase의 증가, phosphocreatine과 ATPase의 소모, ATP 의존성 $Na^{+}/K^{+}$ 펌프작용의 중지, ATP 의존성 $Ca^{2+}$ 유출감소 및 세포내 축적이 관찰된다. 8. $Ca^{2+}$의 축적으로 세포막 교질 침투손상을 주어 수분의 유입을 증가시킴으로써 수포형성, 핵붕괴, 사립체팽화 및 정상세포 구조상실(Zeiosis)이 있다. 결론적으로 CTL 매개성 세포독성작용은 PFP, LT, TNF, 유사 TNF / LT 및 기타 매체를 통한 복합작용이며 세포살해기전은 지속적 대사소모와 정형적 세포구조(핵 및 세포질)의 파괴에 의한 것이다.

• Korean Journal of Food Science and Technology
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• v.50 no.4
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• pp.437-443
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• 2018

Activation of macrophages plays an important role in the host-immune system. In this study, we investigated the functional roles and related signaling mechanism of hot-water extracts of bee pollen (BPW) in RAW 264.7 macrophages. Since BPW did not exert cytotoxicity at concentrations ranging from 62.5 to $250{\mu}g/mL$ in macrophage cells, a concentration of $250{\mu}g/mL$ was used as the maximum dose of BPW throughout subsequent experiments. BPW increased inducible nitric oxide synthase-mediated nitric oxide production in a concentration-dependent manner. Additionally, BPW was found to induce macrophage activation by augmenting the expression of cell surface molecules (cluster of differentiation; CD80/86, and major histocompatibility complex; MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis $factor-{\alpha}$, interleukin-6, and $IL-1{\beta}$) through mitogen-activated protein kinase and nuclear $factor-{\kappa}B$ signaling pathways in RAW 264.7 macrophages. Taken together, our results indicate that BPW could potentially be used as an immunomodulatory agent.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.202.3-203
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• 2003

Calcineurin inhibitors, cyclosporine A (CsA) and tacrolimus (FK506), have been studied extensively regarding their effects on T lymphocytes, but their effects on dendritic cells (DC) are relatively unknown. DC can really capture Ag from dead and dying cells for presentation to MHC class I-restricted CTL. The main targets for the immunosuppressive calcinerin inhibitors, FK506 and CsA. have been considered to be activated T cells, but not antigen presenting cells (APCs). (omitted)

• Journal of fish pathology
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• v.15 no.2
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• pp.83-92
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• 2002

EST analysis was performed to identify stress-responsive and immune-related genes from mud loach (Misgurnus mizolepis), cDNA libraries were constructed with liver, intestine and kidney tissues and randomly chosen clones (216 for liver, 198 for intestine and 224 for kidney) were subjected to automated sequence analysis. Of 638 clones sequenced in totlal, approximalely 25% of ESTs was novel sequences (no match to GenBank) or sequences with high homology to hypothrtical/unknown genes. Several potential stress-responsive biomarker and/or immure-related genes were identified in all the tissues examined. It included lectin, MHC class I/II proteins, proteinase inhibitors, superoxide dismulase, catalase, glutathionc-S. transferase, heat-shock protein, warm temperature acclimation protein, complements, methylrransferasc, zinc finger proteins, macrophage maturation associated protein, and others. This information will offer new possibilities as fundamental baseline data for the molecular genetics and breeding of this species with an emphasis on the development of stress. (and disease)-resistsnt fish.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.205.1-205.1
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• 2003

Bifidobacterium spp. is nonpathogenic. Gram-positive and anaerobic bacteria, which inhabit the intestinal tract of humans and animals. Bifidobacterium spp. plays important roles in human health. However. the influence of exogenous factors on species composition of fecal bifidobacteria is still unclear. In this study, we wished to determine whether presentation of exogenous OVA (10 $\mu\textrm{g}$/$m\ell$) could be enhanced by the culture supernatant of ten Bifidobacterium spp. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.136.2-136.2
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• 2003

Previously, we showed that cyclosporin A and tacrolimus, but not rapamycin, inhibit MHC class I-restricted presentation of exogenous antigen in dendritic cells (DCs). We further characterized the effects of cyclosporin A and tacrolimus on the uptake, processing and cross-presentation of a model antigen, ovalbumin (OVA), in DCs. Treatment of DCs with cyclosporin A or tacrolimus did not inhibit phagocytic activity of DCs. Instead, treatment of DCs with cyclosporin A or tacrolimus inhibited the expression of $H-2K^b$/ molecules complexed with the OVA peptied, SIINFEKL, specifically. (omitted)

• Korean Journal of Microbiology
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• v.38 no.4
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• pp.203-203
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• 2002

Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-α/β) and type II (IFN-γ) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNS mediate direct antiviral effects through induction effector molecules that block viral infection and replications such as 2′, 5-oligoadenylate synthetase (2, 5-OAS). IFNS function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells Is transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-α and IFN-γ are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAKl and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.