• 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.16 no.2
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• pp.126-133
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• 2016

Unlike conventional T cells, innate CD8 T cells develop a memory-like phenotype in the thymus and immediately respond upon antigen stimulation, similar to memory T cells. The development of innate CD8 T cells in the thymus is known to require IL-4, which upregulates Eomesodermin (Eomes). These features are similar to that of virtual memory CD8 T cells and IL-4-induced memory-like CD8 T cells generated in the peripheral tissues. However, the relationship between these cell types has not been clearly documented. In the present study, IL-4-induced memory-like CD8 T cells generated in the peripheral tissues were compared with innate CD8 T cells in terms of phenotype and function. When an IL-4/anti-IL-4 antibody complex (IL-4C) was injected into C57BL/6 mice daily for 7 days, the Eomes^hiCXCR3⁺ CD8 T cell population was markedly increased in the peripheral lymphoid organs and blood. These cells were generated from naïve CD8 T cells or accumulated via the expansion of pre-existing CD44^hiCXCR3⁺ CD8 T cells. Initially, the majority of these CXCR3⁺ CD8 T cells expressed low levels of CD44, which was followed by the conversion to the CD44^hi phenotype. This conversion was associated with the acquisition of enhanced effector function. After discontinuation of IL-4C treatment, Eomes expression levels gradually decreased in CXCR3⁺ CD8 T cells. Taken together, the results of this study demonstrate that IL-4-induced memory-like CD8 T cells generated in the peripheral lymphoid tissues are phenotypically and functionally similar to the innate CD8 T cells generated in the thymus.

• 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.

• Journal of Haehwa Medicine
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• v.17 no.1
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• pp.67-74
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• 2008

Objective: The purpose of this research is to examine the effects of Mahaenggamseok-tang-gagambang (MGTG) on CD3+ T cells, CD4+ T cells and CD8+ T cells in ovalbumin (OVA)-induced asthmatic mice. Methods: C57BL/6 mice were injected, inhaled and sprayed with OVA for 12 weeks (four a week) for asthma induction. Two experimental groups were treated with different concentrations of MGTG (400 mg/kg and 200 mg/kg) extract and cyclosporin A (10 mg/kg) for the later 8 weeks. At the end of the experiment, the mice lung was removed and analyzed CD3+ T cells, CD4+ T cells and CD8+ T cells by flow cytometer. Results: Numbers of CD3+ T cells in lung of the MGTG groups (200, 400 mg/kg) were significantly decreased compared with that of control group. Numbers of CD4+ T cells in lung of the MGTG groups (200, 400 mg/kg) were significantly decreased compared with that of control group. Numbers of CD8+ T cells in lung of the MGTG groups (200, 400 mg/kg) were significantly decreased compared with that of control group. Conclusion: The results of this study suggest that MGTG alleviated asthmatic hyperreactiviry through CD4+ and CD8+ T cells. Further study of relative cytokines is expected.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.438-443
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• 2007

The purpose of this research is to examine the effects of Kamijihwang-tang(KJHT) on CD+4 T cells and CD8+ T cell ovalbumin (OVA)-induced asthmatic mice. C57BL/6 mice were injected, inhaled and sprayed with OVA for 12 weeks (four a week) for asthma induction. Two experimental groups were treated with different concentrations of KJHT (400 mg/kg and 200 mg/kg) extract and cyclosporine A (10 mg/kg) for the later 8 weeks. At the end of the experiment, the mice lung, peripheral lymph node (PLN), and spleen were removed and CD4+ T cells and CD8 + T cells for analyzed by flow cytometer. Number of CD4+ T cells in lung, PLN, spleen of the KJHT group (400 mg/kg) were significantly decreased compared with that of control group. Number of CD8+ T cells in lung, PLN, spleen of the KJHT group (200 mg/kg) were significantly decreased compared with that of control group. The results of this study suggest that KJHT alleviated asthmatic hyperactivity through CD4+ and CD8+ T cells. Further study of relative cytokines is expected.

• IMMUNE NETWORK
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• v.9 no.4
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• pp.127-132
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• 2009

Background: Toll-like receptors (TLRs) play a fundamental role in innate immunity through their capacity to recognize pathogen-associated molecular patterns. Also, TLRs that are expressed in T cells are reported to function as co-stimulatory receptors. However, the functional capacity of TLRs on CD4 T and CD8 T cells has not been directly compared. Here we compared CD4 and CD8 T cell responses to TLR2 ligand plus TCR-mediated stimulation. Methods: TLR2 expression was analyzed on T cell subsets under naive and alloantigen-primed conditions. We analyzed the effects of TLR2 co-stimulation on proliferation and survival of T cell subsets in vitro when stimulated with soluble anti-CD3 in the presence or absence of synthetic ligand $Pam_3CSK_4$. Results: TLR2 expression on CD8 T cells was induced following activation; this expression was much higher than on CD4 T cells. Thus, the molecule was constitutively expressed on Listeriaspecific memory CD8 T cells. Based on these expression levels, proliferation and survival were markedly elevated in CD8 T cells in response to the TLR2 co-stimulation by $Pam_3CSK_4$ compared with those in CD4 T cells. Conclusion: Our data show that TLR2 co-stimulation is more responsible for proliferation and survival of CD8 T cells than for that of CD4 T cells.

• BMB Reports
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• v.49 no.1
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• pp.11-17
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• 2016

The gastrointestinal tract forms the largest surface in our body with constantly being exposed to various antigens, which provides unique microenvironment for the immune system in the intestine. Accordingly, the gut epithelium harbors the most T lymphocytes in the body as intraepithelial lymphocytes (IELs), which are phenotypically and functionally heterogeneous populations, distinct from the conventional mature T cells in the periphery. IELs arise either from pre-committed thymic precursors (natural IELs) or from conventional CD4 or CD8αβ T cells in response to peripheral antigens (induced IELs), both of which commonly express CD8α homodimers (CD8αα). Although lineage commitment to either conventional CD4 T helper (Th) or cytotoxic CD8αβ T cells as well as their respective co-receptor expression are mutually exclusive and irreversible process, CD4 T cells can be redirected to the CD8 IELs with high cytolytic activity upon migration to the gut epithelium. Recent reports show that master transcription factors for CD4 and CD8 T cells, ThPOK (Th-inducing BTB/POZ-Kruppel-like factor) and Runx3 (Runt related transcription factor 3), respectively, are the key regulators for re-programming of CD4 T cells to CD8 lineage in the intestinal epithelium. This review will focus on the unique differentiation process of IELs, particularly lineage re-commitment of CD4 IELs. [BMB Reports 2016; 49(1): 11-17]

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.117-128
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• 2004

Objectives : To examine the effects of Gojineumja on white rats which deteriorated immunity caused by Methotrexate(MTX), first of all, MTX was fed to the rats once a day for 4 day. Methods : After the immune response of the rats are deteriorated, dried extracts of Gojineumja(GJE) mixed in water was fed to the white rats once a day for l4days. The next conclusion was made by examining the rates of B-cells and T-cells of the peripheral blood and the changes in rates of CD4+ T-cells and CD8+ T -cells of the blood sampled from the spleen and peripheral region. Especially the count of CD3+ CD4+ T-cells of the peripheral blood and the count of CD3+ CD4+ T-cells of the spleen the count of CD4+/ CD8+ T-cell of the peripheral blood and the spleen proved the significant effect of increasing immune responses statistically. Results :(1) The following are the summary of the results. (2) The percentage of B lymphocyte of peripheral blood was increased significantly in GJE group as compared with control group. (3) The percentage of CD3+ CD4+ T-cell of peripheral blood was increased significantly in GJE group as compared with control group. (4) The percentage of CD3+ CD8+ T-cell of peripheral blood was not different statistically. (5) The percentage of CD4+/ CD8+ T-cell of peripheral blood was increased significantly in GJE group as compared with control group. (6) The percentage of CD3+ CD4+ T-cell of spleen was increased significantly in GJE group as compared with control group. (7) The percentage of CD3+ CD8+ T-cell was not different statistically. (8) The percentage of CD4+ /CD8+ T-cell was not different statistically. Conclusions : Gojineumja has an effect of increasing immune responses on white rats with deteriorated immunity caused by MTX.

• The Journal of Korean Medicine
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• v.28 no.2 s.70
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• pp.126-136
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• 2007

Objectives : In the present study, the effect of Kuwonsimsin-hwan (KSS) was tested in methotrexate (MTX)-induced immunosuppressed SD rats. Methods : Methotrexate was fed to white rats once a day for 4 days. After the immune responses of the rats deteriorated, dried extracts of Kuwonsimsin-hwan mixed in water was fed to the rats once a day for 14 days. We then measured the number of lymphocytes in peripheral blood and the percentage of B-cells, T-cells, CD3+CD4+T-cells, CD3+CD8+ T-cells and IL-2 productivity sampled from spleen and peripheral region. Results : (1) The number of lymphocytes and the percentage of T-cells and CD3+CD4+ T-cellsin peripheral blood increased significantly in the KSS group as compared with the control group. (2) The percentage of B-cells, CD3+CD8+ T-cells, and CD4+/CD8+ T-cells in peripheral blood were not different statistically. (3) The percentage of T-cells in spleen and IL-2 productivity of spleen cells increased significantly in the KSS group as compared with the control group. (4) The percentage of CD3+CD4+ T-cells in spleen increased in KSS the group as compared with the control group but without statistical significance. (5) The percentage of B-cells, CD3+CD8+ T-cells, and CD4+/CD8+ T-cells in spleen were not different statistically. Conclusion : It is concluded that Kuwonsimsin-hwan has immunostimulating effect on MTX-induced immunosuppressed SD rats.

• 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.