• IMMUNE NETWORK
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• v.8 no.4
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• pp.107-123
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• 2008

It has now been well documented in a variety of models that T regulatory T cells (Treg cells) play a pivotal role in the maintenance of self-tolerance, T cell homeostasis, tumor, allergy, autoimmunity, allograft transplantation and control of microbial infection. Recently, Treg cell are isolated and can be expanded in vitro and in vivo, and their role is the subject of intensive investigation, particularly on the possible Treg cell therapy for various immune-mediated diseases. A growing body of evidence has demonstrated that Treg cells can prevent or even cure a wide range of diseases, including tumor, allergic and autoimmune diseases, transplant rejection, graft-versus-host disease. Currently, a large body of data in the literature has been emerging and provided evidence that clear understanding of Treg cell work will present definite opportunities for successful Treg cell immunotherapy for the treatment of a broad spectrum of diseases. In this Review, I briefly discuss the biology of Treg cells, and summarize efforts to exploit Treg cell therapy for autoimmune diseases. This article also explores recent observations on pharmaceutical agents that abrogate or enhance the function of Treg cells for manipulation of Treg cells for therapeutic purpose.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.8-15
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• 2003

Background: CD30 is a member of TNF receptor family and expressed on lymphocytes and other hematopoietic cells following activation as well as Hodgkin and Reed-Sternberg cells in Hodgkin's lymphoma. In this study, CD30-mediated regulation of cell adhesion molecule expression on normal activated mouse T cells was investigated. Methods: Mouse T cells were activated with anti-CD3 antibody for induction of CD30, which was cross-linked by immobilized anti-CD30 antibody. Results: High level of CD30 expression on T cells was observed on day 5, but only little on day 3 even under culture condition resulting in an identical T cell proliferation, indicating that CD30 expression requires a prolonged stimulation up to 5 days. Cross-linking of CD30 alone altered neither proliferation nor apoptosis of normal activated T cells. Instead, CD30 appeared to promote cell adherence to culture substrate, and considerably upregulated ICAM-1 and, to a lesser extent, ICAM-2 expression on activated T cells, whereas CD2 and CD18 (LFA-1) expression was not affected. None of cytokines known as main regulators of ICAM-1 expression on tissue cells (IL 4, $IFN{\gamma}$ and $IFN{\alpha}$) enhanced ICAM-1 expression in the absence of CD30 signals. On the other hand, addition of $NF-{\kappa}B$ inhibitor, PDTC (0.1 mM) completely abrogated the CD30-mediated upregulation of ICAM-1 expression, but not CD2 and ICAM-2 expression. Conclusion: This results support that CD30 upregulates ICAM-1 expression of T cell and such regulation is not mediated by higher cytokine production but $NF-{\kappa}B$ activation. Therefore, CD30 may play important roles in T-T or T-B cell interaction through regulation of ICAM-1, and -2 expression.

• Molecules and Cells
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• v.43 no.11
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• pp.921-934
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• 2020

Lck-interacting transmembrane adaptor 1 (LIME) has been previously identified as a raft-associated transmembrane protein expressed predominantly in T and B lymphocytes. Although LIME is shown to transduce the immunoreceptor signaling and immunological synapse formation via its tyrosine phosphorylation by Lck, a Src-family kinase, the in vivo function of LIME has remained elusive in the previous studies. Here we report that LIME is preferentially expressed in effector T cells and mediates chemokine-mediated T cell migration. Interestingly, in LIME^-/- mice, while T cell receptor stimulation-dependent proliferation, differentiation to effector T cells, cytotoxic T lymphocyte (CTL) function and regulatory T lymphocyte (Treg) function were normal, only T cell-mediated inflammatory response was significantly defective. The reduced inflammation was accompanied by the impaired infiltration of leukocytes and T cells to the inflammatory sites of LIME^-/- mice. More specifically, the absence of LIME in effector T cells resulted in the reduced migration and defective morphological polarization in response to inflammatory chemokines such as CCL5 and CXCL10. Consistently, LIME^-/- effector T cells were found to be defective in chemokine-mediated activation of Rac1 and Rap1, and dysregulated phosphorylation of Pyk2 and Cas. Taken together, the present findings show that LIME is a critical regulator of inflammatory chemokine-mediated signaling and the subsequent migration of effector T cells to inflammatory sites.

• Restorative Dentistry and Endodontics
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• v.22 no.1
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• pp.374-387
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• 1997

The purpose of this study was to examine the distribution of lymphocyte populations in normal, reversibly inflamed and irreversibly inflamed human dental pulp tissues using flow cytometry. Flow cytometry, with specific antibody and fluorochrome reagent allows us to know cellular properties of hematolymphoid cells by measuring fluorescence of stained cells. Before extirpation of pulps in routine endodontic treatment, the clinical diagnosis were performed by symptom. The extirpated pulp tissues were divided into normal pulp group (N=5), reversible pulpit is group(N=10) and irreversible pulpitis group(N=7). The specimen was placed into RPMI 1640 medium, minced into small pieces, and then digested in medium with collagenase. The cell suspension was resuspended in PBS for monoclonal antibody staining of T lymhocytes(CD3+), B lymphocytes (CD19+), T helper cell (CD4+) and T supressor cell (CD8+). The percentages of cells were counted by FACStar(BD) flow cytometer. Following results were obtained; 1. In the most normal and inflamed pulps, the percentages of T lymphocyte, B lymphocytes, T helper cell and T suppressor/cytotoxic cell were less than 1 % in total counted pulpal cells. 2. The higher percentages of T, B, T helper and T suppressor cells were observed in irreversible pulpitis group as compared with the normal pulp and reversible pulpitis group but the differences between groups were not statistically significant (p>0.05). 3. The percentages of T helper cells (CD4 + cells) were greater than that of T suppressor/cytotoxic cells (CD8 + cells) in the inflamed pulps.

• Parasites, Hosts and Diseases
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• v.31 no.3
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• pp.215-222
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• 1993

In order to establish a useful cell culture system for T gondii we compared the degree of proliferation of T gondii tachyzoites among 8 different cell lines: 2 kinds of normal animal cells (MDCK-canine kidney cells; Vero-monkey kidney cells) and 6 kinds of human tumor cells (A 549, PC 14-lung cancer cells; SNU 1, SNU 16. Mlm 45-stomach cancer cells; HL-60-promyelocytic leukemia cells), through morphological observation and 3H-uracil uptake assay. The degree of susceptibility to infection with T gondii tachyzoites was highest in A 549 and PC 14 cells, medium in Vero, HL-60, MDCK and SNU 1, and lowest in SNU 16 and MBm 45 cells. The kinetics of T gondii multiplication during the post-Infection 60 hours were higllly dependent upon the dose of tachyzoites administered and the duration among the 8 tested fur the growth and multiplication of T gondii in vitro.

• Parasites, Hosts and Diseases
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• v.55 no.6
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• pp.613-622
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• 2017

IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.299-308
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• 2022

T cells are attractive targets for the development of immunotherapy to treat cancer due to their biological features, capacity of cytotoxicity, and antigen-specific binding of receptors. Novel strategies that can modulate T cell functions or receptor reactivity provide effective therapies, including checkpoint inhibitor, bispecific antibody, and adoptive transfer of T cells transduced with tumor antigen-specific receptors. T cell-based therapies have presented successful pre-clinical/clinical outcomes despite their common immune-related adverse effects. Ongoing studies will allow us to advance current T cell therapies and develop innovative personalized T cell therapies. This review summarizes immunotherapeutic approaches with a focus on T cells. Anti-cancer T cell therapies are also discussed regarding their biological perspectives, efficacy, toxicity, challenges, and opportunities.

• Journal of Microbiology and Biotechnology
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• v.27 no.6
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• pp.1189-1197
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• 2017

Lichen-forming fungi are known to have various biological activities, such as antioxidant, antimicrobial, antitumor, antiviral, anti-inflammation, and anti proliferative effects. However, the immunosuppressive effects of Bryoria sp. extract (BSE) have not previously been investigated. In this study, the inhibitory activity of BSE on the proliferation of $CD8^+$ T cells and the mixed lymphocytes reaction (MLR) was evaluated in vitro. BSE was non-toxic in spleen cells and suppressed the growth of splenocytes induced by anti-CD3. The suppressed cell population in spleen cells consisted of $CD8^+$ T cells and their proliferation was inhibited by the treatment with BSE. This extract significantly suppressed the IL-2 associated with T cell growth and $IFN-{\gamma}$ as the $CD8^+$ T cell marker. Furthermore, BSE reduced the expression of the IL-2 receptor alpha chain ($IL-2R{\alpha}$) on $CD8^+$ T cells and CD86 on dendritic cells by acting as antigen-presenting cells. Finally, the MLR produced by the co-culture of C57BL/6 and MMC-treated BALB/c was suppressed by BSE. IL-2, $IFN-{\gamma}$, and CD69 on $CD8^+$ T cells in MLR condition were inhibited by BSE. These results indicate that BSE inhibits the MLR via the suppression of $IL-2R{\alpha}$ expression in $CD8^+$ T cells. BSE has the potential to be developed as an anti-immunosuppression agent for organ transplants.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.171-176
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• 2012

HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as $IFN{\gamma}$, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human ${\beta}2$-defensin (HBD2) in response to $IFN{\gamma}$, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. $IFN{\gamma}$ also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to $IFN{\gamma}$, IL-4 or IL-17A.

• BMB Reports
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• v.40 no.6
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• pp.895-898
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• 2007

The oxygen dependent regulation of DNA replication is an essential property of proliferating mammalian cells. In human T24 bladder cancer cells, several hours of hypoxia leads to reversible DNA replication arrest and re-entry of oxygen induces a burst of replication initiation. This short communication provides strong evidence that PD184352 initiates DNA replication in living hypoxic cells without elevating the oxygen level. PD184352 releases the regular hypoxic replicon arrest, however, at a low intensity compared to the effect of reoxygenation. Moreover, PD184352 shows no effect on normoxically incubated as well as reoxygenated T24 cells.