• 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.10 no.4
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• pp.120-125
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• 2010

Dysfunction of the virus-specific T cells is a cardinal feature in chronic persistent viral infections such as one caused by hepatitis C virus (HCV). In chronic HCV infection, virus-specific dysfunctional CD8 T cells often overexpress various inhibitory receptors. Programmed cell death 1 (PD-1) was the first among these inhibitory receptors that were identified to be overexpressed in functionally impaired T cells. The roles of other inhibitory receptors such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) have also been demonstrated in T-cell dysfunctions that occur in chronic HCV patients. Blocking these inhibitory receptors in vitro restores the functions of HCV-specific CD8 T cells and allows enhanced proliferation, cytolytic activity and cytokine production. Therefore, the blockade of the inhibitory receptors is considered as a novel strategy for the treatment of chronic HCV infection.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.424-431
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• 2024

Among the therapeutic strategies in cancer immunotherapy-such as immune-modulating antibodies, cancer vaccines, or adoptive T cell transfer-T cells have been an attractive target due to their cytotoxicity toward tumor cells and the tumor antigen-specific binding of their receptors. Leveraging the unique properties of T cells, chimeric antigen receptor-T cells and T cell receptor (TCR)-T cells were developed through genetic modification of their receptors, enhancing the specificity and effectiveness of T cell therapy. Adoptive cell transfer of chimeric antigen receptor-T cells has been successful for the treatment of hematological malignancies. To expand T cell therapy to solid tumors, T cells are modified to express defined TCR targeting tumor associated antigen, which is called TCR-T therapy. This review discusses anti-tumor T cell therapies, with a focus on engineered TCR-T cell therapy. We outline the characteristics of TCR-T cell therapy and its clinical application to non-hematological malignancies.

• 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.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.3.1-3.20
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• 2020

Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 therapeutic agents, are now approved by the Food and Drug Administration for treatment of various types of cancer. However, the therapeutic efficacy of ICIs varies among patients and cancer types. Moreover, most patients do not develop durable antitumor responses after ICI therapy due to an ephemeral reversal of T-cell dysfunction. As co-stimulatory receptors play key roles in regulating the effector functions of T cells, activating co-stimulatory pathways may improve checkpoint inhibition efficacy, and lead to durable antitumor responses. Here, we review recent advances in our understating of co-stimulatory receptors in cancers, providing the necessary groundwork for the rational design of cancer immunotherapy.

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

• Journal of Microbiology and Biotechnology
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• v.19 no.2
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• pp.208-214
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• 2009

Steroid hormones have long been known to have a profound influence on the immune system. Although the functions of the nuclear receptors in the development of T cells are fairly well studied, the differential expression of these receptors in T helper cells is poorly understood. Here, we investigated the differential expression of nuclear receptors and coregulators in Th1 and Th2 cells by genome-wide micro array analysis. The result showed that several nuclear receptors and coregulators are differentially expressed in these cells. The result was confirmed by RT-PCR. The result showed that $RXR{\alpha}$ is highly expressed in Th2 cells. Overexpression of $RXR{\alpha}$ in a Jurkat human T cell line induced IL4 but not IFN-${\gamma}$ gene expression, suggesting that $RXR{\alpha}$ plays a selective role in Th1 and Th2 differentiation. In summary, these results suggest that Th1/Th2 differentiation is influenced by differential regulation of nuclear receptors and coregulators.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.5.1-5.15
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• 2020

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

• Korean Journal of Agricultural Science
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• v.47 no.2
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• pp.361-373
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• 2020

Integrins such as lymphocyte function-associated antigen -1 (LFA-1) have an essential role in T cell immunity. Integrin activation, namely, the transition from the inactive conformation to the active one, takes place when an intracellular signal is generated by specific receptors such as T cell receptors (TCRs) and chemokine receptors in T cells. In an effort to explore the molecular mechanisms underlying the TCR-mediated LFA-1 activation, we had previously established a high-throughput cell-based assay and screened a chemical library deposited in the National Institute of Health in the United States. As a result, several hits had been isolated including HIKS-1 (Benzo[b]thiophene-3-carboxylic acid, 2-[3-[(2-carboxyphenyl) thio]-2,5-dioxo-1-pyrrolinyl]-4,5,6,7-tetrahydro-,3-ethyl ester). In an attempt to reveal the mode of action of HIKS-1, in this study, we did drug affinity responsive target stability (DARTS) assay finding that HIKS-1 interacted with the IQ motif containing GTPase activating protein 1 (IQGAP1), a 189 kDa multidomain scaffold protein critically involved in various signaling mechanisms. Furthermore, the cellular thermal shift assay (CETSA) provided compelling evidence that HIKS-1 also interacted with IQGAP1 in vivo. Taken together, it can be concluded that HIKS-1 interferes with the TCR-mediated LFA-1 activation by interacting with IQGAP1 and thereby disrupting the signaling pathway for LFA-1 activation.

• The Journal of Dong Guk Oriental Medicine
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• v.6 no.2
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• pp.99-107
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• 1998

Cyclosporin A(CsA) is a selective immunosuppressive agent that has been credited with improved survival of solid organ allografts. Lymph node of BALB/C mouse administered CsA immunohistochemically observed to understand immunosuppressive effects of CsA on T lymphocytes, IL-2 receptors, and natural killer NK cells in lymph node. CsA orally administered daily for 10days at the dose 45mg/kg/day/. The lymph node were obtained at day 3, 7, and 14 after CsA administration and embedded with paraffin, and then stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly2(CD8), IL-2R(CD25), and NK-1.1(CD56). There were little changes of reactive degree and number of helper T lymphocytes, cytotoxic T lymphocytes, IL-2 receptors, and NK cells at day 3 after CsA administration, but they began to decrease at day 7. These decrease were greatest at day 14. The helper T lymphocytes. cytotoxic T lymphocytes, IL-2 receptors, and NK cells distributed in paracortex and medullary sinus. These results indicated that the secretion of IL-2 began to decrease at day 7 after CsA administration and subsequently to suppress T lymphocytes and NK cell as components of cell-mediated immunity.