IL12p40 Regulates Functional Development of Human CD4+ T Cells

Wang, Xiaobing; Wu, Ting; Zhou, Feng; Shi, Liu; Zhou, Rui; Zhu, Siying; Song, Lu; Feng, Zheng; Wang, Ge; Xia, Bing

doi:10.1097/md.0000000000000613

Cited by 11 publications

(2 citation statements)

References 61 publications

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“…IL-12 and IL-23 play crucial roles in both protective immunity against intracellular pathogens and inflammatory responses. Consequently, comparable alterations in IL-12 and IL-23 transcription levels are observed in various infections caused by viruses, bacteria, and parasites ( Quan et al, 2013 ; Wang et al, 2015 ; Truong et al, 2017 ). Unfortunately, unlike their extensively characterized mammalian counterparts, the cellular sources and unique or overlapping functions of IL-12 and IL-23 in poultry remain poorly understood.…”

Section: Introductionmentioning

confidence: 91%

Differential detection of chicken heterodimeric cytokines, interleukin 12 and 23 using their subunit-specific mouse monoclonal antibodies

Lee,

Kim,

Nam

et al. 2024

Poultry Science

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Section: Introductionmentioning

confidence: 91%

Differential detection of chicken heterodimeric cytokines, interleukin 12 and 23 using their subunit-specific mouse monoclonal antibodies

Lee,

Kim,

Nam

et al. 2024

Poultry Science

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“…3C). Activating naïve CD4 + T cells in the presence of IFN-γ and IL-12 promotes differentiation into type 1 T-helper (Th1) cells, which in turn supports IFN-γ production and increased cytotoxic activity of CD8 + T cells, [29][30][31] as well as further facilitating CD4 + T cell-DC costimulation. Modest increases in GM-CSF, macrophage inflammatory protein-1β, and TNF-α were detected in cocultures with ADP-A2M4CD8 compared with ADP-A2M4 (Supplemental Fig.…”

Section: Activation Of Both Dcs and Adp-a2m4cd8 T Cells Was Increased...mentioning

confidence: 99%

Enhancing Efficacy of TCR-engineered CD4+ T Cells Via Coexpression of CD8α

Anderson¹,

Brilha²,

Weber³

et al. 2023

Journal of Immunotherapy

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Adoptive cell therapy with T cells expressing affinity-enhanced T-cell receptors (TCRs) is a promising treatment for solid tumors. Efforts are ongoing to further engineer these T cells to increase the depth and durability of clinical responses and broaden efficacy toward additional indications. In the present study, we investigated one such approach: T cells were transduced with a lentiviral vector to coexpress an affinity-enhanced HLA class I–restricted TCR directed against MAGE-A4 alongside a CD8α coreceptor. We hypothesized that this approach would enhance CD4+ T-cell helper and effector functions, possibly leading to a more potent antitumor response. Activation of transduced CD4+ T cells was measured by detecting CD40 ligand expression on the surface and cytokine and chemokine secretion from CD4+ T cells and dendritic cells cultured with melanoma-associated antigen A4+ tumor cells. In addition, T-cell cytotoxic activity against 3-dimensional tumor spheroids was measured. Our data demonstrated that CD4+ T cells coexpressing the TCR and CD8α coreceptor displayed enhanced responses, including CD40 ligand expression, interferon-gamma secretion, and cytotoxic activity, along with improved dendritic cell activation. Therefore, our study supports the addition of the CD8α coreceptor to HLA class I–restricted TCR-engineered T cells to enhance CD4+ T-cell functions, which may potentially improve the depth and durability of antitumor responses in patients.

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Novel Therapies and Treatment Strategies for Patients with Inflammatory Bowel Disease

Duijvestein

Battat

Casteele

et al. 2018

Curr Treat Options Gastro

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In the past two decades, tumor necrosis factor antagonist therapy has given clinicians better treatment options. However, not all patients respond to induction therapy with these agents, and of those initially responding, up to 40% ultimately lose response due to suboptimal drug exposure (e.g., caused by immunogenicity), side effects, or other poorly characterized mechanisms. Recently, additional therapies, such as vedolizumab, an integrin blocker that prevents T cell trafficking to the gut, and ustekinumab, an antibody blocking the common p40 subunit of interleukin (IL)-12 and 23, were introduced to the market. In addition, other agents including novel anti-trafficking therapies (e.g., anti-β7 and sphingosine-1-phosphate receptor modulators), antibodies against p19 (unique to IL-23), and small molecules including Janus kinase inhibitors are under investigation in phase II and III trials. Furthermore, the management of IBD has evolved from targeting control of symptoms to suppression of mucosal inflammation. This shift in thinking has been accompanied by the early use of highly effective therapy in poor prognosis patients, accelerated treatment escalation and utilization of a treat to target paradigm approach, and adoption of therapeutic drug monitoring. The treatment landscape for IBD is rapidly evolving with the recent approval of novel biologics as well as several other agents in late phase of clinical development. Moreover, we have started to use agents more intelligently with a focus on risk stratification and early use of highly effective therapy in high-risk patients, treat to target using patient-reported outcomes (PROs), biomarkers, endoscopy, and therapeutic drug monitoring.

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IL12p40 Regulates Functional Development of Human CD4+ T Cells

Abstract: Supplemental Digital Content is available in the text

Cited by 11 publications

References 61 publications

Differential detection of chicken heterodimeric cytokines, interleukin 12 and 23 using their subunit-specific mouse monoclonal antibodies

Differential detection of chicken heterodimeric cytokines, interleukin 12 and 23 using their subunit-specific mouse monoclonal antibodies

Enhancing Efficacy of TCR-engineered CD4+ T Cells Via Coexpression of CD8α

Novel Therapies and Treatment Strategies for Patients with Inflammatory Bowel Disease

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