• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.43 no.6
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• pp.388-394
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• 2017

Objectives: The objective of this study was to investigate the presence of oral lesions in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in a descriptive cross-sectional study, and to establish their presence according to levels of CD4+ cells (including the CD4+/CD8+ cell ratio). Materials and Methods: A total of 75 patients infected with HIV were included. Oral lesions were observed and classified using World Health Organization classification guidelines. Potential correlations between the presence and severity of oral lesions and CD4+ cells, including the CD4+/CD8+ cell ratio, were studied. Results: The most frequent oral lesion detected was oral pseudomembranous candidiasis (80.0%), followed by periodontal disease (40.0%), herpetic lesions (16.0%), hairy leukoplakia (16.0%), gingivitis (20.0%), oral ulceration (12.0%), Kaposi's sarcoma (8.0%), and non-Hodgkin's lymphoma (4.0%). The CD4+ count was <$200cells/mm^3$ in 45 cases (60.0%), between $200-500cells/mm^3$ in 18 cases (24.0%), and >$500cells/mm^3$ in 12 cases (16.0%). The mean CD4+ count was $182.18cells/mm^3$. The mean ratio of CD4+/CD8+ cells was 0.26. All patients showed at least one oral manifestation. Conclusion: There was no correlation between the CD4+/CD8+ cell ratio and the presence of oral lesions. The severity of the lesions was more pronounced when the CD4+ cell count was less than $200cells/mm^3$.

• Molecules and Cells
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• v.26 no.1
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• pp.67-73
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• 2008

Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. ExpreHerpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed $CD4^+$ T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of $CD4^+$ T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts $CD4^+$ T cells into the cornea.

• Molecules and Cells
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• v.28 no.2
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• pp.125-130
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• 2009

Tacrolimus is a widely used T cell targeted immunosuppressive drug, known as a calcineurin inhibitor. However, the exact pharmacological effects of tacrolimus on $CD4^+$ T cells have yet to be elucidated. This study investigated the effects of tacrolimus on $CD4^+$ T cell subsets. Mouse or human $CD4^+$ T cells were cultured with immobilized anti-CD3/CD28 antibodies in the presence of tacrolimus. The cell division of $CD4^+$ T cells was analyzed using a flow cytometer according to the expression of Foxp3. The gene expression patterns of tacrolimus-exposed T cells were examined by quantitative PCR. In the case of conventional $CD4^+$ T cells (Tconv cells), tacrolimus inhibited T cell receptor stimulation-induced cell division. In contrast, the cell division of regulatory $CD4^+$ T cells (Treg cells) was even promoted in the presence of tacrolimus, especially in humans. Tacrolimus did not promote conversion of Tconv to Treg cells in mice. Furthermore, tacrolimus modified the expression levels of Foxp3-regulated T cell receptor signal related-genes, PTPN22 and Itk, in human Treg cells. Immunosuppressive effect of tacrolimus may be attributed to the relatively enhanced proliferation of Treg cells in association with altered gene expression levels of TCR signaling molecules.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.2
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• pp.119-129
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• 2008

Objective: The purpose of this study was to quantify decidual $CD56^+$ and $CD16^+$ NK cell subtype population and to evaluate the correlation between decidual NK cell expression and peripheral $CD56^+$ NK cell expression in women with a history of recurrent abortion and increased peripheral NK cells. Methods: Twenty-nine women with recurrent abortion and elevated peripheral $CD56^+$ NK cell percentage who had chromosomally normal conceptus were included in this study. Thirty-two women with recurrent abortion who had chromosomally abnormal conceptus were used as controls. Distribution of $CD56^+$ and $CD16^+$ NK cells in decidual tissues including implantation sites was examined by immunohistochemical staining. The degree of immunohistochemical staining was interpreted by score and percentage. Results: There was a significant difference in decidual $CD56^+$ NK cell score ($43.6{\pm}24.5$ vs. $23.9{\pm}16.3$ P =0.001) and $CD56^+$ NK cell percentage ($42.1{\pm}11.7$ vs. $33.9{\pm}15.8$ P =0.027) between increased peripheral NK cell group and control group. However, there was no statistically significant difference in decidual $CD16^+$ NK cell score ($18.7{\pm}9.5$ vs. $13.2{\pm}39.4$ P =0.108) and $CD16^+$ NK cell percentage ($24.7{\pm}5.9$ vs. $23.4{\pm}11.7$ P =0.599). There was no significant correlation between decidual NK cell score and peripheral NK cell percentage in increase peripheral NK cell group (peripheral $CD56^+$ NK cell percentage vs. decidual $CD56^+$ NK cell score, r=-0.016, P =0.932, peripheral $CD16^+$ NK cell percentage vs. decidual $CD16^+$ NK cell score, r=0.008, P =0.968). Conclusion: This study shows that $CD56^+$ decidual NK cells are increased in decidua of women exhibiting a history of recurrent abortion with increased $CD56^+$ peripheral NK cell. There was no significant correlation between decidual and peripheral NK cell increment in increase peripheral NK cell group. This study suggests the possibility that decidual NK cells may play an important role in the immune mechanism of recurrent abortion.

• The Journal of Korean Medicine
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• v.31 no.4
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• pp.63-78
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• 2010

Objectives: This study was carried out to know the effects of Gwan-Jul-Bang-7 (hereafter referred to GJB-7) on the inhibition of arthritis induced by collagen on the mouse. Methods: To assess the effects of GJB-7 on mouse with arthritis induced by collagen II, we conducted several experiments such as analysis of cytotoxicity, hepatotoxicity, arthritis index, total cell number of draining lymph nodes and paw joints, value of immunocyte in PBMC (peripheral blood mononuclear cell), DLN (draining lymph node) and paw joint, measurement of cytokine and anti-collagen II, observation of the histological changes of joint. Results: 1. Cytotoxicity against HFC (human fibroblast cells) was not observed in any concentration and hepatotoxicity was not observed in the GJB-7 treated group. 2. The incidence of arthritis significantly decreased. 3. Total cell number of draining lymph nodes significantly increased and total cell number of paw joints significantly decreased. 4. The percentage of $CD8^+$ cells in PBMC (peripheral blood mononuclear cell) significantly increased. The percentage of $CD3^+/CD69^+$, and $CD3^+/CD49b^+$ cells in PBMC significantly decreased. 5. The percentage of $CD19^+,\;CD3^+$, and $CD4^+/CD25^+$ cells in DLN (draining lymph nodes) significantly increased. The percentage of $B220^+/CD23^+$ cells in DLN significantly decreased. 6. The percentage of $CD3^+,\;CD4^+$, and $CD11b^+/Gr-1^+$ cells in paw joints significantly decreased. 7. The production of TNF-$\alpha$, IL-6, and MCP-1 significantly decreased. 8. Anti-collagen II in serum significantly decreased. 9. With the hematoxylin and eosin stain, inflammation of joint decreased. Under Masson's trichrome stain, the cartilage destruction and synovial cell proliferation and the expression of collagen fibers decreased. Conclusions: Comparison of the results for this study showed that GJB-7 had immunomodulatory effects. So we expect that GJB-7 could be used as an effective drug for not only rheumatoid arthritis but also another auto-immune diseases.

• Journal of the korean academy of Pediatric Dentistry
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• v.35 no.4
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• pp.597-606
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• 2008

Resorption of alveolar bone in periodontitis is due to excessive differentiation and activation of osteoclasts. Bacterial antigens causing periodontitis activates CD4 T cells, which leads to expressing RANK ligand (RANKL) on CD4 T cells. RANKL binds RANK on preosteoclasts or osteoclasts, and enhances the differentiation preosteoclasts into osteoclasts and the activation of mature osteoclasts. CD137, one of TNF receptor (TNFR) family, expressed on activated T cells binds with CD137 ligand (CD137L) on antigen presenting cells. Cross-linking of CD137 by CD137L acts as T cell co-stimulatory signals and, therefore, enhances the activation of T cell. In this study, I elucidated the biological responses of CD137L on (pre)osteoclasts and RANKL on T cells in the context of in vivo interaction between T cells and osteoclasts. RAW264.7, murine monocytic cells, constitutively express CD137L. Ligation of CD137L with anti-CD137L mAb inhibited RANKL-induced osteoclast formation in a dosedependent manner. Bone marrow cells are expressed CD137L by the treatment with M-CSF. Cross-linking of CD137L abolished M-CSF/ RANKL-evoked the formation of multi-nucleated osteoclasts. Both mouse CD4 and CD8 T cells are expressed RANKL following their activation. Ligation of RANKL with OPG, the decoy receptor for RANKL, inhibited both CD4 and CD8 T cell proliferation. These effects were attributed to RANKL-induced apoptosis. These data indicate that CD137L and RANKL on osteoclasts and T cells, respectively provide them with inhibitory signal.

• Korean Journal of Animal Reproduction
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• v.27 no.3
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• pp.225-231
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• 2003

Transgenic mice containing Diphtheria Toxin-A (DT-A) gene fused to proximal lck promoter sequences was used for analysis of DT-A gene expression and thymocyte development. The diphtheria toxin gene was expressed in thymus, spleen and liver of transgenic mice confirmed by RT-PCR and Northern blotting. A FACS analysis with thymocyte cell surface antigens antibodies (CD4 and CD8) showed that the number of peripheral mature single positive thymocytes ($CD4^{+}\;and\;CD8^{+}$ cells) T-cells was severely reduced in transgenic mice compared to that in the non-transgenic littermates. A relative portion of $CD8^{+}$ single positive thymocytes was about 33.2% in transgenic peripheral T-cells while 50.6% in wild type. Reduction of $CD4^{+}$ cell numbers in transgenic mice was observed (5.9% in transgenic versus 10.3% in non-transgenic). The data from analysis of these transgenic mice indicate that the proximal lck promoter regulated the expression of DT-A gene at high level in developing thymocytes and the DT-A disrupted developing thymocytes in transgenic mice.

• Biomedical Science Letters
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• v.27 no.4
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• pp.329-333
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• 2021

We previously identified that tumor cells genetically modified with a 4-1BBL co-stimulatory molecule had anticancer effects in a CT26 mouse colorectal tumor model. To identify the distinction between immune cells in a mouse tumor model treated with tumor cells genetically modified with 4-1BBL or β-gal, we examined the immune cells in CT26-WT, CT26-βgal, and CT26-4-1BBL tumor bearing mice 21 days after tumor cell administration. The CD8+ T cells population in mice treated with tumor cells genetically modified with 4-1BBL was significantly increased on day 21 compared to that of tumor cells genetically modified with β-gal in the spleen and tumor tissue. The CD4+ T cell population was not different between the two mice groups. The Foxp3+CD25^high CD4 T cell population decreased on day 21 in tumor tissues, but the decrease was not significant. We also found that CD8 T cells had pivotal roles in inhibiting tumor growth by treating mice with ant-CD4 and CD8 antibodies. These results suggest that tumor cells genetically modified with 4-1BBL could inhibit tumor growth by affecting on CD8 T lymphocytes.

• The Journal of Korean Society of Virology
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• v.30 no.1
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• pp.83-99
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• 2000

A defective HIV-1 helper virus DNA, pHyPC, was assembled by deleting the RNA packaging signal, env, nef and the 3'LTR sequences. HIV-1 like virus particles that carry the HIV-1 receptor, CD4 were generated by co expression of pHyPC and plasmid DNAs encoding different chimeric CD4 proteins. The CD4 particles, sharing the CD4 ectodomain, precisely fused to different membrane anchors. CD4(+) particles specifically bound to HIV-1 Env expressing cells, but any signs of infection into these cells were not detected. Binding was only partially blocked by either polyclonal anti-CD4 antibodies or by high concentrations of soluble CD4. Surprisingly, CD4(+) particles also adsorbed to HeLa, CHO, NIH3T3 and COS-7 cells in the absence of HIV-1 Env expression. Adsorption was comparable in strength and speed to the highly specific CD4-Env interaction. CD4(-) particles exhibited only background levels of binding. Cell binding was CD4. dependent, but it was independent of the cell type from which the CD4(+) particles originated. Interestingly, CD4-dependent/Env-independent binding was only found when CD4 was present on virus particles. This suggests that the micro-environment of CD4 on virus particles uniquely expose this new cell binding activity. Its high affinity could explain in part why infection of Env(+) cells by CD4(+) particles was not detected. Further experiments will be required to evaluate whether this strong membrane interaction could represent one step in the multiple-step viral entry process.

• Animal cells and systems
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• v.3 no.3
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• pp.331-336
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• 1999

p56$^{Ick}$, a cytoplasmic protein tyrosine kinase of the src family, is non-covalently associated with the cell surface coreceptors CD4 and CD8, which are expressed on thymocytes and mature T cells. The coreceptor protein plays an important role during the differentiation of thymocytes and the activation of T cells. DNA constructs were designed to study the roles of CD4 and CD8 during the differentiation of thymocytes. One is a chimeric cDNA which consists of coding regions for the extracellular domain of CD8a and the transmembrane and cytoplasmic domain of CD4. The other is the same chimeric cDNA but with a point mutation converting Cys to Ala in the Ick-binding site to disrupt the association. We confirmed that the CD8a/CD4 chimeric molecule bound to Ick more efficiently than the wild type CD8a protein. However, the chimeric protein with the Cys$leftrightarro$Ala mutation did not associate with Ick. The results suggest a possibility that the CD8a/CD4 chimeric protein may behave like a CD4 protein in associating with Ick and that it may deliver a signal inside the cell in a similar manner, Analysing effects of the mutant CD8a/CD4 chimeric protein expression in developing thymocytes will elucidate the role of Ick during the determination of CD4/CD8 cell lineages.