Triggering of CD99 on monocytes by a specific monoclonal antibody regulates T cell activation

Laopajon, Witida; Pata, Supansa; Takheaw, Nuchjira; Surinkaew, Sirirat; Khummuang, Saichit; Kasinrerk, Watchara

doi:10.1016/j.cellimm.2018.10.012

Cited by 11 publications

(11 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Monocytes and B cells are antigen presenting cells and express co-stimulatory molecules including HLA-ABC (MHC class I), HLA-DR (MHC class II), CD80, and CD86, which contribute to T cell activation [ 47 , 48 ]. Downregulation of these co-stimulatory molecules was demonstrated to attenuate T cell functions [ 49 , 50 ]. We observed that the CB1 agonist ACEA significantly reduced the expression levels of CD86 on B cells, whereas the CB2 agonist GW833972A decreased HLA-ABC expression levels on monocytes, which might have resulted in reduction of T cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid Receptor 1 Agonist ACEA and Cannabinoid Receptor 2 Agonist GW833972A Attenuates Cell-Mediated Immunity by Different Biological Mechanisms

Takheaw

Jindaphun

Pata

et al. 2023

Cells

Self Cite

View full text Add to dashboard Cite

Cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) are components in the endocannabinoid system that play significant roles in regulating immune responses. There are many agonists for the cannabinoid receptors; however, their effects on T cell regulation have not been elucidated. In the present study, we determined the effects of the CB1 selective agonist ACEA and the CB2 selective agonist GW833972A on T cell responses. It was found that both agonists impaired anti-CD3 monoclonal antibody induced T cell proliferation. However, ACEA and GW833972A agonists down-regulated the expression of activation markers on CD4+ and CD8+ T cells and co-stimulatory molecules on B cells and monocytes in different manners. Moreover, only GW833972A suppressed the cytotoxic activities of CD8+ T cells without interfering in the cytotoxic activities of CD4+ T cells and NK cells. In addition, the CB2 agonist, but not CB1 agonist, caused the reduction of Th1 cytokine production. Our results demonstrated that the CB1 agonist ACEA and CB2 agonist GW833972A attenuated cell-mediated immunity in different mechanisms. These agonists may be able to be used as therapeutic agents for inducing T cell hypofunction in inflammatory and autoimmune diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Cannabinoid Receptor 1 Agonist ACEA and Cannabinoid Receptor 2 Agonist GW833972A Attenuates Cell-Mediated Immunity by Different Biological Mechanisms

Takheaw

Jindaphun

Pata

et al. 2023

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…Daratumumab, a monoclonal antibody targeting CD38, has also been successfully used for eradication of minimal residual disease in relapsed T-acute lymphoblastic leukaemia (Cox et al, 2016). CD99 has been shown to be overexpressed on T-acute lymphoblastic leukaemia cells and is considered to be a reliable detector of the disease (Laopajon et al, 2019). It has been reported that CD99 monoclonal antibody (mAb) MT99/3 can inhibit T-cell activation (Xie et al, 2021) and determine the suitability of CD99 as a therapeutic target.…”

Section: Monoclonal Antibodymentioning

confidence: 99%

The pathogenesis and development of targeted drugs in acute T lymphoblastic leukaemia

Chen

Xin

Wei

et al. 2023

British J Pharmacology

View full text Add to dashboard Cite

Acute lymphoblastic leukaemia (ALL) is mainly classified into acute T-and Blymphoblastic leukaemia according to the source of its lymphocytes, thymus and bone. Among them, the incidence of adult T-cell accounts for about 25% of adult acute lymphoblastic leukaemia, but the degree of malignancy is high and the treatment rate and prognosis are poor. At this stage, there are few targeted drugs and the commonly used broad-spectrum chemotherapeutic drugs have poor efficacy and many adverse drug reactions. Understanding and investigating the pathogenesis of T-acute lymphoblastic leukaemia is very important for further developing new targeting drugs and improving existing drugs. Dysregulated signalling pathways are the main aetiological factors of T-acute lymphoblastic leukaemia. They play crucial roles in promoting tumour initiation, progression, drug design and therapy responses. This is primarily because signalling pathways are indispensable for many cellular biological processes, including tumour growth, migration, invasion, metastasis and others. As a result, small molecule inhibitors targeting the major kinase components of the signalling pathway have received a lot of attention and have been developed and evaluated in preclinical models and clinical trials. Already marketed drugs are also being repurposed in combination therapies to further improve efficacy and overcome tumour cell resistance. In this review, we have aimed to examine the latest and most classical signalling pathways in the aetiology of T-acute lymphoblastic leukaemia and shed light on potential targets for novel therapeutic agents to act on.

show abstract

“…In addition, we analyzed the cellular composition by mass cytometry and plasma markers by the Olink assay during treatment of P1. The major effect on the innate immune system was found for NK cells, which upregulated the activation markers CD45, CD52, and CD99 [57][58][59][60][61]. Notably, JAK inhibitor treatment has previously been shown to increase the degranulation capacity of NK cells, which could contribute to protection against viral infections and cancer in patients with STAT1 GOF [62].…”

Section: Statement Of Principal Findingsmentioning

confidence: 99%

Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors

et al. 2022

View full text Add to dashboard Cite

Purpose The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors. Methods Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans. Results Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-ɣ and CXCL10 were downregulated. Conclusions The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.

show abstract

Triggering of CD99 on monocytes by a specific monoclonal antibody regulates T cell activation

Cited by 11 publications

References 37 publications

Cannabinoid Receptor 1 Agonist ACEA and Cannabinoid Receptor 2 Agonist GW833972A Attenuates Cell-Mediated Immunity by Different Biological Mechanisms

Cannabinoid Receptor 1 Agonist ACEA and Cannabinoid Receptor 2 Agonist GW833972A Attenuates Cell-Mediated Immunity by Different Biological Mechanisms

The pathogenesis and development of targeted drugs in acute T lymphoblastic leukaemia

Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors

Contact Info

Product

Resources

About