Fine tuning subsets of CD4+ T cells by low-dosage of IL-2 and a new therapeutic strategy for autoimmune diseases

Zhao, Zhen; Zhang, Xiaojuan; Su, Lili; Xu, Le; Zheng, Yong; Sun, Jian

doi:10.1016/j.intimp.2018.01.042

Cited by 23 publications

(14 citation statements)

References 84 publications

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“…17 ). Clinical research has shown that IL-2 therapy is effective in promoting tolerance in autoimmune and inflammatory conditions, primarily by enhancing the development and maintenance of regulatory T cells 18 . In this study, we additionally report that an increase in plasmacytoid DCs, also known for their tolerogenic immune properties against innocuous antigens 19,20 , to be unique to infants with PST.…”

Section: Resultsmentioning

confidence: 99%

Mass cytometry reveals cellular fingerprint associated with IgE+ peanut tolerance and allergy in early life

et al. 2020

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IgE-mediated peanut allergic is common, often serious, and usually lifelong. Not all individuals who produce peanut-specific IgE will react upon consumption of peanut and can eat the food without adverse reactions, known as sensitized tolerance. Here, we employ high-dimensional mass cytometry to define the circulating immune cell signatures associated with sensitized tolerance and clinical allergy to peanut in the first year of life. Key features of clinical peanut allergic are increased frequency of activated B cells (CD19 hi HLADR hi), overproduction of TNFα and increased frequency of peanut-specific memory CD4 T cells. Infants with sensitized tolerance display reduced frequency but hyper-responsive naive CD4 T cells and an increased frequency of plasmacytoid dendritic cells. This work demonstrates the utility and power of high-dimensional mass cytometry analysis to interrogate the cellular interactions that are associated with allergic sensitization and clinical food allergy in the first year of life.

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Section: Resultsmentioning

confidence: 99%

Mass cytometry reveals cellular fingerprint associated with IgE+ peanut tolerance and allergy in early life

et al. 2020

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“…While IL-2 promotes the proliferation and function of Tregs, Teffs, and NK cells, it induces Tregs at much lower concentrations because Tregs constitutively express the high-affinity IL-2Rαβγ c receptor, whereas Teffs and NK cells mostly express the intermediate-affinity IL-2Rβγ c receptor (25). Capitalizing on this feature, inducing preferential expansion of Treg populations via 30.4 Overwijk…”

Section: Autoimmune Diseasesmentioning

confidence: 99%

Engineering IL-2 to Give New Life to T Cell Immunotherapy

2021

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Interleukin-2 (IL-2) is integral to immune system regulation. Its opposing immunostimulatory and immunosuppressive actions make it an attractive therapeutic target for cancer and autoimmune diseases. A challenge in developing IL-2-directed anticancer therapies has been how to stimulate effector T cells (Teffs) without inducing regulatory T cells (Tregs) in the tumor microenvironment; conversely, IL-2 therapy for autoimmune diseases requires Treg induction without further stimulation of Teffs. High-dose IL-2 is approved for melanoma and renal cell carcinoma, but its therapeutic value is limited by a need for frequent dosing at specialist centers, its short half-life, severe toxicity, and a lack of efficacy in most patients. Re-engineered IL-2 therapeutics are designed to have longer in vivo half-lives, target specific IL-2 receptor conformations to stimulate specific T cell subsets, or localize to target tissues to optimize efficacy and reduce toxicity. We discuss recent studies that elucidate the potential of newly engineered IL-2-based therapeutics for cancer and autoimmune diseases. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…Similarly, IL-2, a cytokine that is required for the function of regulatory T cells may not only induce a pro-regulatory environment but could also reduce the likelihood of ADA developing to the drug. This mechanism may contribute to the effectiveness of low-dose IL-2 therapy in autoimmune disease (93). Conversely, IL-2 is also capable of enhancing the function of effector T cell responses and has been used at high doses in the treatment of viral and oncological disease (94).…”

Section: Drug Function As a Determinant Of Immunogenicitymentioning

confidence: 99%

T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation–Updated Consensus and Review 2020

et al. 2020

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Fine tuning subsets of CD4+ T cells by low-dosage of IL-2 and a new therapeutic strategy for autoimmune diseases

Cited by 23 publications

References 84 publications

Mass cytometry reveals cellular fingerprint associated with IgE+ peanut tolerance and allergy in early life

Mass cytometry reveals cellular fingerprint associated with IgE+ peanut tolerance and allergy in early life

Engineering IL-2 to Give New Life to T Cell Immunotherapy

T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation–Updated Consensus and Review 2020

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