• IMMUNE NETWORK
• /
• v.14 no.2
• /
• pp.89-99
• /
• 2014

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-${\gamma}$ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 ${\rightarrow}$ BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 ${\rightarrow}$ BALB.B GVHD model, we showed that the production of IFN-${\gamma}$ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-${\gamma}$ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

• The Journal of Korean Medicine
• /
• v.24 no.3
• /
• pp.1-10
• /
• 2003

Background : Asthma is a chronic inflammatory disorder under immunological influence. Gamichunggumgangwha-tang (CG, Jiaweiqingjinjianghuo-tang) and Gamiyukmigiwhang-tang (YM, Jiaweiliuweidihuang-tang) are herbal tonics for asthma from traditional herbal medicine. Objective : To evaluate the effect of CG and YM on immune cell & serum OA-specific IgE in broncho-alveolar lavage fluid (BALF) in a rat asthma model. Materials and Methods : Rats were sensitized with OA; at day I sensitized group and CG and YM groups were systemically immunized by subcutaneous injection of 1mg OA and 300mg of Al(OH)3 in a total volume of 2ml. At the same time, 1 ml of 0.9% saline containing $6{\times}10^9$ B. pertussis bacilli was injected by Lp. 14 days after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerosol containing 2% (wt/vol) OA. A day after local immunization, BALF was collected from the rats. Rats were orally administered with each of CG and YM extract for 14 days since the day after local immunization. Lymphocyte, CD4＋ T cell and CD8＋ T cell counts, CD4＋/CD8＋ ratio in BALF, change of serum OA-specific IgE level, CD4＋ T cell and CD8＋ T cell percentages in the peripheral blood were measured and evaluated. Results : CG and YM showed an alleviating effect on asthmatic responses of rats. CG decreased total cell, lymphocyte, CD4＋ T cells in BALF, and serum OA-specific IgE level as compared with the control group. YM decreased lymphocytes as compared with the control group. CD4＋/CD8＋ ratio in BALF from the CG and YM groups and serum OA-specific IgE level from the YM group didn't show any significant variation from the control group. Conclusion : CG alleviated asthmatic hyperreactivity of the immune system through CD4＋ T cells and serum IgE. Further the study of this immune system modulating mechanism is expected.

• Biomolecules & Therapeutics
• /
• v.15 no.4
• /
• pp.218-223
• /
• 2007

T cell proliferation is a pivotal to an effective immune response. Cyclin-dependent kinase (cdk) inhibitor, $p27^{kip1}$ is degraded to initiate T cell expansion. In this study, we show that although the expression of $p27^{kip1}$ protein was down-regulated, that of $p21^{cip1}$, another cdk inhibitor, was up-regulated in $CD8^+$ T cells following in vitro stimulation. Ex vivo gB antigen-stimulation following HSV immunization increased $p21^{cip1}$ positive cells that co-expressed IFN-$\gamma$. Moreover, $p21^{cip1}$ was co-expressed with IFN-${\gamma}$ in E7 antigen-stimulated $CD8^+$ T cells, whereas $p27^{kip1}$ was not. Our findings imply a role of $p21^{cip1}$ proteins in antigen-induced effector $CD8^+$ T cells differentiation in vivo.

• IMMUNE NETWORK
• /
• v.1 no.3
• /
• pp.236-243
• /
• 2001

Background: An immunological approach for aging mechanism appears to be important. Lymphocyte subsets analysis in peripheral blood is widely performed to assess the immune status and to diagnose and monitor various diseases. Some lymphocyte subsets are known to change with age, but only few data about age-related reference ragnes for these subsets in healthy individuals have been reported. So we attempted to report reference ranges for these subsets in each age group and review changes of the results with age for the secondary studies about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement (VDJ) including recombination activating genes (RAG-1 and RAG-2). Methods: Lymphocyte subset analysis was performed on 302 subjects, 189 males and 113 females with age group of all decades of life. Two color direct immunofluorescene flow cytometry (FCM) was done using $Simultest^{TM}$ IMK-Lymphocyte kit (Becton Dickinson, USA), $FACScan^{TM}$ (Becton Dickinson, USA) and $FACSCalibur^{TM}$ (Becton Dickinson, USA). Lymphocyte subsets analysed were T ($CD3^+$) and B cells ($CD19^+$), helper/inducer T ($CD4^+$) and suppressor/cytotoxic T cells ($CD8^+$), helper/suppressor ($CD4^+/CD8^+$) ratio and natural killer (NK) cells ($CD3^-CD16^+/CD56^+$). The absolute numbers of each subset were calculated from total lymphocyte counts. Data collected was analysed using SAS 6.12. A P-value of < 0.05 was considered significant. Results: We reported the counts and percentages of lymphocyte and these subsets in each age group. There were no statistically significant differences between male and female subjects. The percentage of $CD4^+$ T cells, and the count of NK cells did not show the significant difference among the various age groups. The age-related changes observed in our study were as following: 1) a decrease in the percentages of T cells, B cells and $CD8^+$ T cells ; 2) a decrease in the counts of B cells and $CD8^+$ T cells ; 3) an increase in the percentage and count of NK cells ; and 4) an increase in the $CD4^+/CD8^+$ ratio. Conclusion: The characteristics of aging process appeared to be showing a marked decrease of lympocyte subsets T and B cells as well as T8 ($CD8^+$). The age-related increase of the percentage of cells bearing NK marker can be interpreted as a compensatory consequence to cope with the decrease of T cells related to the thymic involution. These changes with age appeared to be for the secondary study about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.8
• /
• pp.4671-4673
• /
• 2013

Objectives: To study variation in T lymphocyte subgoups and its clinical significance in non-small cell lung cancer (NSCLC). Methods: Levels of CD3+, CD4+, CD8+, CD4+/CD8+, NK and Treg cells in peripheral blood of NSCLC cases and healthy adults were determined by flow cytometry. Results: CD3+, CD4+ and CD4+/CD8+ ratio and NK cells in NSCLCs were decreased significantly in comparison with the control group (P < 0.01), and decreased with increase in the clinical stage of NSCLC, while CD8+ cells demonstrated no significant change (P > 0.05). Treg cells were significantly more frequent than in the control group (P < 0.01), and increased with the clinical stage of NSCLC. Conclusion: The cellular immune function of the NSCLC patients is lowered. It is important to detect change of T lymphocyte subgroups by flow cytometry for the diagnosis, treatment and prognostic assessment of NSCLC patients.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.1
• /
• pp.265-271
• /
• 2014

Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive $CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively. $CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of $CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of $CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of $CD8^+$ T cells. Furthermore, in vivo neutralization of $CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating $CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy.

• Biomolecules & Therapeutics
• /
• v.30 no.5
• /
• pp.418-426
• /
• 2022

Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1⁺ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8⁺ T cells having CD8⁺CD44⁺CD62L^low phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.

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

• IMMUNE NETWORK
• /
• v.10 no.5
• /
• pp.164-172
• /
• 2010

Background: We tested the hypothesis that dengue haemorrhagic fever (DHF) is associated with a $T_H1$-skewed immune response as opposed to dengue fever (DF). Methods: We estimated intracellular (in T-cells) and serum levels of designate $T_H1/T_H2$ cytokines [interferon-${\gamma}$ (IFN-${\gamma}$), interleukin-4 (IL-4), and tumor necrosis factor-${\alpha}$] and macrophage inflammatory protein-$1{\alpha}$ (MIP-$1{\alpha}$) at admission, 48h, and day 5 in 20 adults with dengue (DF=10, DHF=10) and 10 dengue-naive healthy controls. Results: At admission, intracellular IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells and proportion of MIP-$1{\alpha}$-positive CD8+ T-cells were significantly higher in patients with DHF [7.21 (5.36~10.81) vs. 3.04 (1.75~4.02); p=0.011 and 6.2% (3.2~8.2%) vs. 2.4% (2.0~3.6%); p=0.023]. The latter showed a significant positive correlation with IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells (Spearman's rho=0.64; p=0.003), percentage-change in haematocrit (rho=0.47; p=0.048), and serum alanine amino-transferase level (rho=0.61; p=0.009). Conclusion: We conclude that DHF is associated with a $T_H1$-skewed immune response. Further, MIP-$1{\alpha}$ in CD8+ T-cells is an important immunologic correlate of disease severity in dengue.

• Journal of Ginseng Research
• /
• v.47 no.1
• /
• pp.155-158
• /
• 2023

In the present study, we investigated whether treatment with KRG improve the parameters of immune activity such as the cytotoxicity, populations of CD4⁺ CD8⁺T cell, CD3^-CD172^-CD8⁺ NK cell and CD172⁺ monocyte as well as natural cytotoxicity receptors such as Nkp46, Nkp44, Nkp30. In results, KRG significantly increased these immune activities. These results indicate that KRG has distinct immuneenhancing effects by increasing the roles of T cells and NK cell in porcine.