• IMMUNE NETWORK
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• v.20 no.1
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• pp.2.1-2.19
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• 2020

Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. This stem cell-like CD8 T-cell subset has been also observed in both mouse and human tumor models. Most importantly, in both chronic viral infection and tumor models, the proliferative burst of Ag-specific CD8 T cells driven by PD-1-directed immunotherapy comes exclusively from this stem cell-like CD8 T-cell subset. Therefore, a better understanding of the mechanisms how CD8 T-cell subsets are regulated during chronic viral infection and cancer is required to improve the current immunotherapies that restore the function of exhausted CD8 T cells. In this review, we discuss the differentiation of virus-specific CD8 T cells during chronic viral infection, the characteristics and function of CD8 T-cell subsets, and the therapeutic intervention of PD-1-directed immunotherapy in cancer.

• IMMUNE NETWORK
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• v.7 no.4
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• pp.173-178
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• 2007

Background: We studied the role for expression of CD40 and CD40L by CD4 and CD8 T cells in the generation of CD8 T cell response to minor histocompatibility antigen, H60. H60 is a cellular antigen to which CD8 responses require CD4 T cell help. Methods: CD40- or CD40L-deficient mice were adoptively transferred with normal CD4 or CD8 T cells or with memory CD4 or CD8 T cells, and were immunized with male H60 congenic splenocytes to induce CD8 T cell response to H60. Peripheral blood CD8 T cell from the immunized mice were stained with the H60 tetramer. Results: CD8 T cell response to H60 was not induced in both CD40- and CD40L-deficient mice. Adoptive transfer of $CD40^{+/+}$ CD8 T cells into CD40-deficient mice did not compensate the defect in inducing CD8 T cell response to H60, while the H60-specific CD8 T cells were activated in the CD40-deficient mice that were adoptively transferred with $CD40^{+/+}$ CD4 T cells. Adoptive transfer of $CD40L^{+/+}$ CD4 T cells into CD40L-deficient mice induced primary CD8 T cell response for H60 and the presence of $CD40L^{+/+}$ CD4 T cells was required even for memory CD8 T cells response to H60. Conclusion: Our results suggest that the CD40-CD40L interaction mediates the delivery of CD4 T cell help to naive and memory H60-specific CD8 T cells. While the expression of CD40L by CD4 T cells is essential, signaling through CD40 on CD8 T cells is not required for the induction of CD8 T cell response to H60.

• IMMUNE NETWORK
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• v.23 no.5
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• pp.41.1-41.21
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• 2023

CD4 and CD8 T cells are key players in the immune response against both pathogenic infections and cancer. CD4 T cells provide help to CD8 T cells via multiple mechanisms, including licensing dendritic cells (DCs), co-stimulation, and cytokine production. During acute infection and vaccination, CD4 T cell help is important for the development of CD8 T cell memory. However, during chronic viral infection and cancer, CD4 helper T cells are critical for the sustained effector CD8 T cell response, through a variety of mechanisms. In this review, we focus on T cell responses in conditions of chronic Ag stimulation, such as chronic viral infection and cancer. In particular, we address the significant role of CD4 T cell help in promoting effector CD8 T cell responses, emerging techniques that can be utilized to further our understanding of how these interactions may take place in the context of tertiary lymphoid structures, and how this key information can be harnessed for therapeutic utility against cancer.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.441-446
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• 1994

The responsiveness of $CD8^+$ T-cell subpopulation according to serum-containing and serum-free conditions were investigated. Cells are freshly isolated from spleen of mature adult BALB/C mice between 13-20 weeks of age. $CD8^+$ T cells in serum-free conditions produce small amounts of IL-2, while significant amounts of IFNr following activation when compared the results of serum-containing conditions. These data indicate that serum-derived factors may play an important role in the alternations of $CD8^+$ T cell responsiveness.

• 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.

• Journal of Life Science
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• v.25 no.6
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• pp.686-692
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• 2015

Cancer is subject to dynamic interactions between contrary immune reactions that drive both tumor growth and suppression. Forkhead box p3 positive T cells (Foxp3 positive T cells) might support tumor promotion, while CD8 positive T cells might protect the host. The present study examined the distributions of CD8- and Foxp3-positive T cells and CD8 positive T cells/ Foxp3 positive T cells ratio in skin squamous cell carcinoma (SCC) and its precancerous lesions; it also compared this with data for basal cell carcinoma (BCC). Iimmunohistochemical staining for CD8 and Foxp3 was conducted in 20 cases of SCC, Bowen's disease (BD), actinic keratosis (AK) and BCC. The BD and SCC cases exhibited significantly increased numbers of both CD8- and Foxp3-positive T cells in their advancing regions compared with the AK and BCC cases, and the BD cases exhibited significantly lower CD8 positive T cells / Foxp3 positive T cells ratio in these regions than did the AK and BCC cases. There was no significant difference in both T cells and the ratio between BD and SCC. The degree of both T cells infiltration differed between the advancing and central areas in SCC and BCC. Immune micro-environments differ between cutaneous squamous cell tumors and BCC and differ as well among tumor compartments.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1991.06a
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• pp.20-20
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• 1991

악성종양의 발생과 진행에 면역 방어기능이 중요한 역할을 하리라는 가설은 모두가 공감하는 사실이다. 이중 T-lymphocyte와 Natural killer cell (이하 NK cell이라함)은 종양 면역학에 특히 중요한 임파구로 이런 임파구의 혈액분포양상은 면역방어기능을 짐작할 수 있는 간접적인 자료가 될 수 있다. 저자들은 치료전 두경부 악성종양환자에서 혈액을 채취하여 T-lymphocyte와NK cell의 분포양상을 검사하고, 방사선치료 환자에서는 NK cell activity를 측정하였기에 다음과 같은 결과를 보고하는 바이다. 1) 두경부 악성 종양 환자군에서 CD3+ cell은 감소하고 NK cell은 증가하며 CD4/CD8 비율은 변화가 없었다. 2) 병변이 진행되면서 CD3+ cell과 CD4+ cell은 감소하고 NK cell은 증가하였으며 CD4/CD8 비율의 변화는 없었다. 3) 방사선치료에 의해 CD3+ cell과 CD4+ cell, CD4/CD8 비율은 감소하였고, NK cell과CD8+cell은 증가하였다. 4) 방사선치료에 의한 CD4/CD8 비율의 감소와, CD8+ cell의 증가는 NK cell의 증가에 의한 것이라 추정되고, NK cell을 제외하면 CB4/CD8 비율의 변화는 없었다. 5) 방사선치료 환자에서 NK cell activity는 증가하였고, 이런 증가가 T-lymphocyte기능의 감소를 보상해 주고 있었다.

• Molecules and Cells
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• v.39 no.7
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• pp.515-523
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• 2016

Long-term immunity to many viral and bacterial pathogens requires$ CD8^+$ memory T cell development, and the induction of long-lasting$ CD8^+$ memory T cells from a $na{\ddot{i}}ve$, undifferentiated state is a major goal of vaccine design. Formation of the memory$ CD8^+$ T cell compartment is highly dependent on the early activation cues received by $na{\ddot{i}ve}$ $CD8^+$ T cells during primary infection. This review aims to highlight the cellularity of various niches within the lymph node and emphasize recent evidence suggesting that distinct types of T cell activation and differentiation occur within different immune contexts in lymphoid organs.

• The Journal of Pediatrics of Korean Medicine
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• v.21 no.1
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• pp.227-252
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• 2007

Objectives : In order to investigate the effect of Bobitang on SD rats with deteriorated immunity caused by methotrexate. Methods : The test sample were dosed once a day for 14 days by gastric gavage at a dosage 1,000, 500 and $250mg/kg/10m{\ell}$ from 2 days after last MTX-dosing, and the changes on body weight and gains, spleen weight and total blood leukocyte numbers, total lymphocyte numbers, the percentage of B-cell, T-cell, CD3+CD4+ T-cell, CD3+CD8+ T-cell and CD4+/CD8+ T-cell ratios in the blood and spleen were observed. Results : The changes on body weight gains, the spleen weight, the total blood leukocyte numbers, the total lymphocyte numbers in the blood and spleen, the ratio of T-cell in the blood and spleen, the ratio of CD3+CD4+ T-cell in the blood and spleen were increased significantly in BBT Extracts groups as compared with control group. The ratio of B-cell in the blood and spleen was not increased significantly in BBT Extracts groups as compared with control group. The percentage of CD3+CD8+ T-cell in the blood and spleen was decreased significantly in BBT Extracts groups as compared with control group. The ratio of CD4+/CD8+ T-cell in blood and spleen was increased significantly in BBT Extracts group as compared with control group. Conclusions : According to the above results, Bobi-Tang has an effect of increasing immune responses on SD rats with deteriorated immunity caused by methotrexate.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.118-125
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• 2012

CD40-CD40L-mediated help from CD4 T cells is essential to induce primary CD8 T cell responses specific to the non-inflammatory cell-based antigen H60. In this study, using H60 as a model antigen, we generated recombinant vaccinia viruses (rVVs) expressing the H60 CD8 epitope and investigated whether CD4 help was required to activate the CD8 T cell response specific to the virally expressed H60. The immune response after infection with rVVs expressing H60 was similar to that after immunization with H60 congenic splenocytes, with a peak frequency of H60-specific CD8 T cells detected in the blood on day 10 post-infection. A CD8 T cell response specific for virally derived H60 was not induced in CD4-depleted mice, but was in CD40-deficient mice. These results provide insights into the characterization of the CD8 T cell response specifically for antigens originating from cellular sources compared to viral sources.