In a recent letter in the Journal of Allergy and Clinical Immunology, researchers from Benaroya Research Institute (BRI), Children's Hospital of Philadelphia (CHOP), and Massachusetts General Hospital (MGH) identified the first food antigen-specific T cell from a patient with milk allergy who developed milk-triggered eosinophilic esophagitis (EoE). The results from this study provide additional evidence that EoE is mediated by food antigen-specific T cells.

EoE is a disease that affects both children and adults and is triggered when a patient ingests an allergenic food. It is accompanied by an increase in eosinophils, a type of immune cell that often plays a role in allergic responses, as well as T cells in the esophagus. The immune cell invasion of the esophagus results in inflammation, tissue damage, and fibrosis, which can cause difficulty swallowing, esophageal obstruction, and esophageal dysfunction. Traditionally, EoE has been managed in the clinic as a food allergy, with treatment revolving around dietary avoidance of food triggers. However, this is the first time that a food antigen-specific T cell has been identified in an EoE patient.

Because of their expertise in single cell RNA-sequencing and T cell receptor (TCR) analysis, Drs. Karen Cerosaletti and Alex Hu at BRI collaborated with the researchers at CHOP who had collected genomic data from T cells from the blood of a patient with confirmed EoE milk allergy. Upon analyzing these data, they identified a milk-specific TCR in the population of pathogenic T helper 2 (TH2) cells, a T cell subset previously observed in the esophageal tissue of EoE patients. They also found that these milk-specific TH2 cells had elevated expression of genes related to activation, cytotoxicity, exhaustion, and regulation, as well as increased interferon signaling. Altogether, this evidence links the detection of milk antigen by an antigen-specific T cell to eosinophilic recruitment, allergic response, and inflammation in EoE.

“With the data that their colleagues collected from an EoE milk allergy patient, Drs. Cerosaletti and Hu we were able to confirm that this case of EoE was mediated by T cell recognition of milk antigen,” said BRI President, Dr. Jane Buckner. “Food antigen triggers likely exist for many patients with EoE. This study lays out an approach for the investigation of these other food allergies in EoE, for which we have little knowledge.”

For more information about BRI, visit BenaroyaResearch.org.

In a new study published in the Journal of Allergy and Clinical Immunology led by Benaroya Research Institute (BRI) and Seattle Children’s Research Institute in collaboration with the University of Washington School of Medicine and the University of Wisconsin, researchers discovered why individuals with allergic asthma may have reduced susceptibility to COVID-19 and an important mechanism by which allergic inflammation diminishes SARS-CoV-2 infection, despite well-known susceptibilities to other respiratory viral infections. 

Allergic diseases such as asthma are characterized by type-2 inflammation in the airways. BRI’s Naresh Doni Jayavelu, PhD, and the research team looked at mechanisms whereby type-2 inflammation in the airway surprisingly protects against SARS-CoV-2 in children. The study utilized bronchial airway cells from carefully characterized children with and without asthma obtained from the biorepository of Dr. Jason Debley, investigator at the Center for Immunity and Immunotherapies at Seattle Children’s Research Institute. The Debley Lab team then used the cells to conduct SARS-CoV-2 infection experiments in their biosafety level 3 (BSL-3) facility using an organotypic ex vivo airway epithelial model system. Results demonstrated that viral replication was lower in airway epithelial cells from children with allergic asthma compared to their healthy counterparts, and that increasing the level of type-2 inflammation in the epithelium could dramatically impair viral replication. 

“This was a highly collaborative research effort that revealed important molecular and clinical insights by which people with allergic asthma are likely protected from SARS-CoV-2 infection,” said Dr. Jayavelu. “Early epidemiologic studies reported conflicting findings on the association of asthma with COVID-19 adverse outcomes. However, now we are seeing that it is other pulmonary disease (such as COPD) that confer risk for worse COVID-19, but surprisingly allergy and allergic asthma can confer unexpected protection.”

The findings also illustrate a notable mechanism of intrinsic protection against SARS-CoV-2. 

“To my knowledge, this is perhaps the most compelling demonstration of a mechanism of intrinsic protection against SARS-CoV-2. We know antibody responses after vaccine or natural infection are protective, but this mechanism protects in the absence of prior exposure to the virus,” said Matthew Altman, MD, BRI affiliate investigator and co-author on the study. 

Since the study findings are based on in vitro cell culture experiments, Dr. Jayavelu and Dr. Altman are now investigating to what degree type-2 inflammation decreases viral replication and severe disease in a large observational cohort that was enrolled at the beginning of the pandemic to more fully understand the clinical impact of their results. 

This research was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and other sources. It builds on a previous study that set the groundwork for a hypothetical mechanism of protection. For more information on BRI and its asthma research, visit benaroyaresearch.org.

BRI's Erik Wambre's discovery of the Th2A cell could be a big step toward stopping allergies. The cell, which only appears in people with allergies is currently being used as a biomarker of allergy in a study where participants are slowly exposed to the allergen. Next, Dr. Wambre is interested in working to find the molecule that will block the Th2A cells to treat not just one allergy, but all of them.

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