• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7681-7684
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• 2013

Background: Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. Materials and Methods: We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. Results: There were 29 cancer-related deaths during the follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors for patient survival. Conclusions: We found a significant positive correlation between HLA-G expression and the number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T lymphocytes.

• IMMUNE NETWORK
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• v.15 no.4
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• pp.186-190
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• 2015

Cytomegalovirus (CMV) infection in healthy individuals is usually asymptomatic and results in latent infection. CMV reactivation occasionally occurs in healthy individuals according to their immune status over time. T cell responses to CMV are restricted to a limited number of immunodominant epitopes, as compared to responses to other chronic or persistent viruses. This response results in progressive, prolonged expansion of CMV-specific $CD8^+$ T cells, termed 'memory inflation'. The expanded CMV-specific $CD8^+$ T cell population is extraordinarily large and is more prominent in the elderly. CMV-specific $CD8^+$ T cells possess rather similar phenotypic and functional features to those of replicative senescent T cells. In this review, we discuss the general features of CMV-specific inflationary memory T cells and the factors involved in memory inflation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3815-3819
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• 2012

The CD4+CD25+ regulatory T cell (Treg) is a special kind of T cell subset. Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer. Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance. The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma (HCC). A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods. Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status.The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ($18.8%{\pm}1.26%$) was found to be significantly higher than that in normal mice ($9.99%{\pm}1.90%$) (P<0.01 ). Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed. Anti-tumour immunity was suppressed, and this might be associated with the increase of Tregs. Our observations suggest that the CD4+CD25+Treg/CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer.

• Biomedical Science Letters
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• v.18 no.3
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• pp.210-217
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• 2012

Oncolytic viral vectors have shown good candidates for cancer treatment but have many limitations. To improve the therapeutic potential of oncolytic vaccinia virus, we developed a recombinant vaccinia virus expressing the 4-1BBL co-stimulatory molecule or CCL21. 4-1BBL and CCL21 expression was identified by FACS analysis and immunoblotting. rV-4-1BBL vaccination shows significant tumor regression compared to rV-LacZ, but rV-CCL21 shows rapid tumor growth compared to rV-LacZ in the poorly immunogenic B16 murine melanoma model. 4-1BBL expression resulted in the increase of the number of CD8+ T cells and especially the increase of effector (CD62L-CD44+) CD8+ T cells. These data suggest 4-1BBL may be the potential target for enhancement of tumor immunotherapy.

• Molecules and Cells
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• v.44 no.11
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• pp.795-804
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• 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.

• Preventive Nutrition and Food Science
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• v.8 no.1
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• pp.7-12
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• 2003

This study examined the effect of pine needle distillate (Pinus densiflora Sieb. et Zucc) on the immune system and hematological parameters. C57BL/6 male mice weighing 20 ~21 g were divided into 3 groups and intraperitonially injected with either 200 $\mu$L of saline (control), 50% diluted (P50) or 100% pine needle distillate (P100) once a day for 24 days. At the end of the experiment, the mice were anesthetized by ether and peripheral blood was collected from the femoral artery and the spleen was excised. Spleen weight decreased significantly (p<0.001) in the pine needle groups compared to the control group. The blood was used for a complete blood count and flow cytometrical analysis after immunofluorescence staining. The pine needle distillate dose-dependently decreased the CD4$^{＋}$/CD8 sup ＋/ ratio (p <0.05), and showed a tendency to increase the mean FSC (forward scatter) values of the CD8$^{＋}$T cells, while decrease the values of the CD4$^{＋}$T cells. There were no significant differences in WBC, RBC and platelet counts among the three groups, but hemoglobin and hemoglobin-related parameters and platelet volume increased and red blood cell volumes decreased with the administration of the pine needle distillate. These results suggest that the pine needle distillate may have immunosuppressive effects.

• The Korea Journal of Herbology
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• v.26 no.2
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• pp.1-10
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• 2011

Objective ： Lonicera japonica contains anti complementary polysaccharides and polyphenolic compound. Among these polyphenolic substances, chlorogenic acid is the major active component of this plant. However, the immunological mechanisms for these activities, have not been elucidated, nor the active components. To clarify immunomodulatory effects of those we examined the relationship between the activity of CD8+ T cell-mediated lysis and the frequency of cytokine profiles in spleen, thymus (especially IFN-${\gamma}$, IL-4, GM-CSF etc.) expressing CD8+ T cells activated by IL-2. Methods : To study immunomodulatory effects ethyl acetate fraction from Lonicera japonica, chlorogenic acid on cytokine gene expression from spleen, thymus cells, RT-PCR was performed after quantitative normalization for each gene by a densitometry using ${\beta}$-actin gene expression. A modified standard $^{51}Cr$-release assay was used to measure cytotoxic activities of cytotoxic T cells. Spleen, thymus cells from NOD mice were stained with CD3, CD4, CD44, CD69 in staining buffer and analyzed by two color flow cytometry. Results : We showed that ethyl acetate fraction from Lonicera japonica in combination with IL-2 resulted in a significant enhancement of PCR products for IFN-${\gamma}$, IL-4, IL-10, GM-CSF, IL-6 and cytotoxtic CD8+ T cell proportion in spleen and thymus T cells in NOD mice. This suggests that IFN-${\gamma}$, IL-6 like IL-4 may be acting as a regulatory rather than proinflammatory cytokine. Conclusions : In conclusion, based on the results of the present study which showed that ethyl acetate fraction from Lonicera japonica and chlorogenic acid upregulating cytokine gene expression in spleen and thymus, we are tempted to speculate that some of the therapeutic efficacies such as anti-diabetic activity of Lonicera japonica are due to the immunomodulatory its ethylacetate fraction and chlorogenic acid.

• IMMUNE NETWORK
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• v.7 no.4
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• pp.186-196
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• 2007

Background: Although IL-12 has been widely accepted to playa central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body. Methods: To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly ($A_{DL}$-lactic-co-glycolic acid) (PLGA). Results: We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific $CD4^+\;and\;CD8^+$ T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of $CD8^+$ T cell response was not detectable when $CD4^+$ T cell knockout mice were subjected to vaccination, indicating that the enhancement of the $CD8^+$ T cell response by IL-12EM is dependent on $CD4^+$ T cell "help". Conclusion: Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection.

• Clinical and Experimental Pediatrics
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• v.54 no.5
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• pp.207-211
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• 2011

Purpose: This study was conducted to investigate the immune responses of children with moderate and severe novel influenza A virus (H1N1) pneumonia, and to compare their clinical and immunological findings with those of control subjects. Methods: Thirty-two admitted patients with H1N1 pneumonia were enrolled in the study. The clinical profiles, humoral and cell-mediated immune responses of the 16 H1N1 pneumonia patients who were admitted to the pediatric intensive care unit (severe pneumonia group), 16 H1N1 pneumonia patients admitted to the pediatric general ward (moderate pneumonia group) and 13 control subjects (control group) were measured. Results: Total lymphocyte counts were significantly lower in patients with H1N1 pneumonia than in the control group (P=0.02). The number of CD4+ T lymphocytes was significantly lower in the severe pneumonia group ($411.5{\pm}253.5/{\mu}L$) than in the moderate pneumonia ($644.9{\pm}291.1/{\mu}L$, P=0.04) and control ($902.5{\pm}461.2/{\mu}L$, P=0.01) groups. However, the number of CD8+ T lymphocytes was significantly higher in the severe pneumonia group ($684.2{\pm}420.8/{\mu}L$) than in the moderate pneumonia ($319.7{\pm}176.6/{\mu}L$, P=0.02) and control ($407.2{\pm}309.3/{\mu}L$, P=0.03) groups. The CD4+/CD8+ T lymphocytes ratio was significantly lower in the severe pneumonia group ($0.86{\pm}0.24$) than in the moderate pneumonia ($1.57{\pm}0.41$, P=0.01) and control ($1.61{\pm}0.49$, P=0.01) groups. The serum levels of immunoglobulin G, immunoglobulin M and immunoglobulin E were significantly higher in the severe pneumonia group than in the 2 other groups. Conclusion: The results of this study suggest that increased humoral immune responses and the differences in the CD4+ and CD8+ T lymphocyte profiles, and imbalance of their ratios may be related to the severity of H1N1 pneumonia in children.

• Tuberculosis and Respiratory Diseases
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• v.68 no.4
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• pp.218-225
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• 2010

Background: Bronchoalveolar lavage (BAL) is a useful technique to recover lower airway fluid and cells involved in many respiratory diseases. Miliary tuberculosis is potentially lethal, but the clinical manifestations are nonspecific and typical radiologic findings may not be seen until late in the course of disease. In addition, invasive procedures are often needed to confirm disease diagnosis. This study analyzed the cells and the T-lymphocyte subset in BAL fluid from patients with miliary tuberculosis to determine specific characteristics of BAL fluid that may help in the diagnosis of miliary tuberculosis, using a less invasive procedure. Methods: On a retrospective basis, we enrolled 20 miliary tuberculosis patients; 12 patients were male and the mean patient age was $40.5{\pm}16.2$ years. We analyzed differential cell counts of BAL fluid and the T-lymphocyte subset of BAL fluid. Results: Total cells and lymphocytes were increased in number in the BAL fluid. The percentage of CD4+ Tlymphocytes and the CD4/CD8 ratio in BAL fluid were significantly decreased and the percentage of CD8+ T-lymphocytes was relatively higher. These findings were more prominent in patients infected with the human immunodeficiency virus (HIV). In the HIV-infected patients, the proportion of lymphocytes was significantly higher in BAL fluid than in peripheral blood. There were no significant differences between the BAL fluid and the peripheral blood T-lymphocytes subpopulation. Conclusion: BAL fluid in patients with miliary tuberculosis demonstrated lymphocytosis, a lower percentage of CD4+ T-lymphocytes, a higher percentage of CD8+ T-lymphocytes, and a decreased CD4/CD8 ratio. These findings were more significant in HIV-infected subjects.