• 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.

• 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.

• YAKHAK HOEJI
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• v.48 no.4
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• pp.241-246
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• 2004

Mercury is a widespread metal and consequently there are large populations that currently exposed to low levels of mercury. Endotoxin is a component of the gram-negative bacteria and promotes inflammatory responses. The present study was designed to determine the impact of mercury on lymphocytes phenotype populations and endotoxin-induced inflammatory cytokine expressions in immune organ, spleen and thymus. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercuric chloride in drinking water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The dose-range of mercury used did not cause hepatotoxicity. Mercury at 7.5 and 37.5 ppm dose-dependently decreased CD3$^{+}$ T lymphocytes in spleen; both CD4$^{+}$ and CD8$^{+}$ single positive lymphocyte populations were decreased. Exposure to 7.5 and 37.5 ppm of mercury decreased the CD8$^{+}$ T lymphocyte population in the thymus, whereas double positive CD4$^{+}$ / CD8$^{+}$ and CD4$^{+}$ thymocytes were not altered. Mercury altered LPS-induced inflammatory cytokine gene expressions such as, tumor necrosis factor $\alpha$, interferon ${\gamma}$, and interleukin-12 in spleen and thymus. Results indicated that decreases in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immune-modulative effects of inorganic mercury.ganic mercury.

• IMMUNE NETWORK
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• v.20 no.3
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• pp.20.1-20.15
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• 2020

Memory CD8+ T cells in the immune system are responsible for the removal of external Ags for a long period of time to protect against re-infection. Naïve to memory CD8+ T cell differentiation and memory CD8+ T cell maintenance require many different factors including local environmental factors. Thus, it has been suggested that the migration of memory CD8+ T cells into specific microenvironments alters their longevity and functions. In this review, we have summarized the subsets of memory CD8+ T cells based on their migratory capacities and described the niche hypothesis for their survival. In addition, the basic roles of CCR7 in conjunction with the migration of memory CD8+ T cells and recent understandings of their survival niches have been introduced. Finally, the applications of altering CCR7 signaling have been discussed.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.4
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• pp.363-372
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• 2020

Gardenia jasminoides (GJ) is a widely used herbal medicine with anti-inflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJ_EtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJ_EtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJ_HEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJ_HEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited I_ORAI1 and interleukin-2 production in CD3/CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4⁺ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.8.1-8.13
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• 2023

CD8⁺ T cells are activated by TCRs that recognize specific cognate Ags, while NK-cell activation is regulated by a balance between signals from germline-encoded activating and inhibitory NK receptors. Through these different processes of Ag recognition, CD8⁺ T cells and NK cells play distinct roles as adaptive and innate immune cells, respectively. However, some human CD8⁺ T cells have been found to express activating or inhibitory NK receptors. CD8⁺ T-cell populations expressing NK receptors straddle the innate-adaptive boundary with their innate-like features. Recent breakthrough technical advances in multi-omics analysis have enabled elucidation of the unique immunologic characteristics of these populations. However, studies have not yet fully clarified the heterogeneity and immunological characteristics of each CD8⁺ T-cell population expressing NK receptors. Here we aimed to review the current knowledge of various CD8⁺ T-cell populations expressing NK receptors, and to pave the way for delineating the landscape and identifying the various roles of these T-cell populations.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.9.1-9.15
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• 2023

Cancer immunotherapies continue to face numerous obstacles in the successful treatment of solid malignancies. While immunotherapy has emerged as an extremely effective treatment option for hematologic malignancies, it is largely ineffective against solid tumors due in part to metabolic challenges present in the tumor microenvironment (TME). Tumor-infiltrating CD8⁺ T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T-cell recruitment to the tumor site and hyporesponsive effector functions via T-cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8⁺ T-cell activation, migration, effector functions, and persistence in tumors. Therefore, targeting the mitochondrial metabolism of adoptively transferred T cells has the potential to greatly improve the effectiveness of cancer immunotherapies in treating solid malignancies.

• Journal of Veterinary Clinics
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• v.40 no.3
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• pp.203-208
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• 2023

A 13-year-old neutered male mixed-breed dog presented with generalized lymphadenopathy and erythematous cutaneous lesions in the ear pinnae. Fine-needle aspiration cytology of the lymph nodes revealed small to intermediate lymphocytes with a "hand mirror" configuration as the predominant cell type. Histopathological analysis of the lymph node showed an infiltrate of CD3-positive small lymphocytes compressing the follicles against the capsule owing to neoplastic cell expansion. Flow cytometric analysis revealed a homogeneous population of CD3+/CD4-/CD5+/CD8-/CD21+/CD34-/CD45- cells in both the peripheral blood and aspirated lymph nodes, which supports the diagnosis of T-zone lymphoma. Laboratory tests revealed lymphocytosis (14,144 cells/µL) in the peripheral blood. However, contrary to expectations, the bone marrow examination revealed no evidence of lymphocytic infiltration. T-zone lymphoma is an indolent lymphoma with a long survival period, and knowledge of its characteristics may affect disease staging and prognosis evaluation. Therefore, peripheral blood count as a sole screening tool for bone marrow metastasis should be used with caution.

• Korean Journal of Veterinary Research
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• v.61 no.3
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• pp.21.1-21.6
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• 2021

Canine T-zone lymphoma (TZL) is a mature T-cell lymphoma in dogs. The diagnosis and sub-classification are impossible without biopsy or immunophenotyping by flow cytometry. An 11-year-old, spayed, female Golden Retriever presented with lymph node enlargement. Clinical examination was consistent with canine multicentric lymphoma. However, immunophenotyping revealed positive for CD3, CD4, CD5, CD8, CD21, TCRαβ, and MHCII but negative for CD34, CD45, CD79a, and TCRγδ. Histopathology revealed lymphocytes expanding to the cortex-preserving architecture and thinning of the nodal capsule, and CD3 positive but PAX-5 negative. Owing to the indolent nature of TZL, careful monitoring approach without clinical intervention was utilized.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.96-102
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• 2003

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccines induce very potent systemic anti-tumor immunity in preclinical and clinical models. Our previous phase I clinical trial in patients with metastatic renal cell carcinoma (RCC) has demonstrated both immune cell infiltration at vaccine sites and T cell-mediated delayed-type hypersensitivity (DTH) response to whole tumor cell vaccines. Methods: To investigate the immune responses to autologous genetically- modified tumor cell vaccines, tumor-specific $CD8^+$ T cell lines were generated from peripheral blood lymphocytes (PBL) of a RCC patient 1.24 by repeated in vitro stimulation with either B7.1-transduced autologous RCC tumor cells or B7.1-transduced autologous tumor cells treated with interferon gamma ($IFN{\gamma}$), and cloned by limiting dilution. Results: Among several RCC-specific cytotoxic T lymphocytes (CTLs), a $CD4^+/CD8^+$ double positive T cell clone (17/A2) appeared to recognize $IFN{\gamma}$-treated autologous RCC restricted by HLA-B39. The 17/A2 also recognized other HLA-B39 positive RCC tumor cells after $IFN{\gamma}$ treatment. Conclusion: These results demonstrate that autologous RCC vaccination successfully generates the tumor-specific CTL 17/A2, and suggest that the presentation and recognition of the tumor antigen by the 17/A2 might be upregulated by $IFN{\gamma}$.