Newly identified T cell subsets in mechanistic studies of food immunotherapy

Sampath, Vanitha; Nadeau, Kari

doi:10.1172/jci124605

Cited by 36 publications

(26 citation statements)

References 121 publications

(114 reference statements)

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“…It has been hypothesized that consumption of multiple allergens simultaneously increases polyclonal T cell memory subsets, increasing Th1 receptor Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 15 December 2021 diversity, leading to enhanced protection against potentially allergenic proteins compared to double or single food early intervention. (35) Our study had lower dropout rates and safety issues compared to other multifood introduction studies (18). We believe regular daily dosing of small amounts of mixed food proteins was key to the success of this study.…”

Section: Discussionmentioning

confidence: 56%

Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy

Quake¹,

Liu²,

D’Souza³

et al. 2021

Preprint

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The incidence and prevalence of food allergy (FA) are increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants particularly in those at high or low risk of atopy are still unclear. This 1-year study evaluated the safety of early introduction of single foods (milk, egg, or peanut), vs. two foods (milk/egg, egg/peanut, milk/peanut), vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/fish/soy at low, medium, or high doses) vs no early introduction in infants between 4-6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity with standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixture was 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least 6 months of age. Results demonstrate that infants at either high or low risk for atopy were able to tolerate early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that early introduction of foods, particularly simultaneous mixtures of many allergenic foods is efficacious for preventing FA and can occur safely.

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Section: Discussionmentioning

confidence: 56%

Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy

Quake¹,

Liu²,

D’Souza³

et al. 2021

Preprint

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“…240 ► Newly identified T cell subsets in mechanistic studies of food immunotherapy. 241 Satpathy AT et al 242 describe the use of scATAC-seq with a droplet-based method on a widely used single-cell 10X Chromium platform to discover cell types and regulatory DNA elements in complex tissues. They performed scAT-AC-seq using bone marrow and blood samples to characterize the chromatin landscape of cell subtypes and their differentiation trajectories.…”

Section: Atac-seqmentioning

confidence: 99%

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery

Hu‐Lieskovan

Bhaumik

Dhodapkar

et al. 2020

J Immunother Cancer

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Since the publication of the Society for Immunotherapy of Cancer’s (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in the field is the fact that only a minority of patients respond to immunotherapy, especially those therapies that rely on endogenous immune activation such as checkpoint inhibitors and vaccination due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Therefore, the development of robust biomarkers for each immunotherapy strategy, enabling rational patient selection and the design of precise combination therapies, is key for the continued success and improvement of immunotherapy. In this document, we summarize and update established biomarkers, guidelines, and regulatory considerations for clinical immune biomarker development, discuss well-known and novel technologies for biomarker discovery and validation, and provide tools and resources that can be used by the biomarker research community to facilitate the continued development of immuno-oncology and aid in the goal of durable responses in all patients.

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“…Allergen-specific Th2 cells constitute a critical component in this cascade of events. Th2 cells are broadly defined by the expression of the transcription factor GATA3 and the secretion of cytokines IL-4, IL-5, and IL-13, which promote class-switching of B cells to IgE and recruitment of eosinophils as well as other effector cells 6,7 . Recent studies have highlighted subtypes of Th2 cells with specialized functions in the context of allergy, including effector memory (e.g.…”

Section: Introductionmentioning

confidence: 99%

Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells

Monian

Ruiter

et al. 2021

Preprint

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Food allergy affects an estimated 8% of children in the US, with increasing severity and global prevalence. Oral immunotherapy (OIT) is a recently approved treatment with outcomes ranging from sustained tolerance to food allergen to no apparent benefit. The immunological underpinnings that influence clinical outcomes of OIT still remain largely unresolved. Using single cell RNA sequencing and paired TCRa/b sequencing, we assessed the transcriptomes of CD154+ and CD137+ peanut-reactive T helper cells from 12 peanut-allergic patients longitudinally throughout OIT. We observed expanded populations of cells expressing Th1, Th2, and Th17 signatures that further separated into six clonally distinct subsets, including a Tfh1-like, a Tfh2-like, a Th2A-like, and a Th2reg-like subset. Four of these subsets demonstrated convergence of TCR sequences, suggesting antigen-driven T cell fate. Although we observed suppression during OIT of Th2 and Th1 gene signatures within effector clonotypes, Tfh clonotypes were unaffected. We also did not observe significant clonal deletion or induction among the antigen reactive T cells characterized. Positive outcomes were associated with larger decrease of Th2 signatures in Th2A-like cells, while treatment failure was associated with high baseline inflammatory gene signatures that were unmodulated by OIT. These signatures, including expression of OX40, OX40L, STAT1, and GPR15, were most clearly present in Th1 and Th17 clonotypes, but were also more broadly detected across the CD154+ CD4 population. These results demonstrate that differential clinical response is associated both with pre-existing trait characteristics of the CD4 immune compartment and with susceptibility to modulation by OIT.

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Newly identified T cell subsets in mechanistic studies of food immunotherapy

Abstract: cuss the T cell-specific immune monitoring techniques that have made these discoveries possible.

Cited by 36 publications

References 121 publications

Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy

Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery

Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells

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