B cells modulate mouse allergen-specific T cells in nonallergic laboratory animal-care workers
Esther Dawen Yu, … , Ricardo da Silva Antunes, Alessandro Sette
Esther Dawen Yu, … , Ricardo da Silva Antunes, Alessandro Sette
Published February 22, 2021
Citation Information: JCI Insight. 2021;6(4):e145199. https://doi.org/10.1172/jci.insight.145199.
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Research Article Immunology

B cells modulate mouse allergen-specific T cells in nonallergic laboratory animal-care workers

Abstract

Understanding the mechanisms of allergen-specific immune modulation in nonallergic individuals is key to recapitulate immune tolerance and to develop novel allergy treatments. Herein, we characterized mouse-specific T cell responses in nonallergic laboratory animal-care workers before and after reexposure to mice. PBMCs were collected and stimulated with developed peptide pools identified from high-molecular-weight fractions of mouse allergen extracts. Sizable CD4 T cell responses were noted and were temporarily decreased in most subjects upon reexposure, with the magnitude of decrease positively correlated with time of reexposure but not the duration of the break. Interestingly, the suppression was specific to mouse allergens without affecting responses of bystander antigens. Further, PBMC fractioning studies illustrated that the modulation is unlikely from T cells, while B cell depletion and exchange reversed the suppression of responses, suggesting that B cells may be the key modulators. Increased levels of regulatory cytokines (IL-10 and TGF-β1) in the cell culture supernatant and plasma mouse-specific IgG4 were also observed after reexposure, consistent with B cell–mediated modulation mechanisms. Overall, these results suggest that nonallergic status is achieved by an active, time-related, allergen-specific, B cell-dependent regulatory process upon reexposure, the mechanisms of which should be detailed by further molecular studies.

Authors

Esther Dawen Yu, Luise Westernberg, Alba Grifoni, April Frazier, Aaron Sutherland, Eric Wang, Bjoern Peters, Ricardo da Silva Antunes, Alessandro Sette

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Figure 3

Characterizing the key regulatory cell population.

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Characterizing the key regulatory cell population. (A) T cell–APC mixing...
(A) T cell–APC mixing study (n = 4). T cell responses from pre-break (PRB) samples and after reexposure (ARE) samples without mixing are shown (white) as control. T cells and APCs were separated from samples of both visits and mixed with each other. T cell responses from all 4 mixing combination samples are shown (shaded bar). (B) B cell depletion and add-back study. PRE samples are shown in white and ARE samples are represented by shaded bars. T cell responses from original PRE and ARE samples without B cell depletion are shown on the left as controls (n = 6). The T cell response of the same 6 samples after B cell depletion are shown in the middle. Four subjects had their B cells depleted first and then added back to the original samples; those T cell responses are shown on the right. (C) B cell exchange study (n = 4). T cell responses from the original PRE samples and ARE samples are shown in white as control. The shaded bars represent T cell responses from samples with B cells separated first, and then either added back to the original samples (middle) or exchanged between PRE and ARE samples (right). Antigen-specific T cell responses with positive AIM signals (4-1BB+OX40+) are represented by numbers per million of CD4 T cells. Normality of distribution was accessed by Shapiro-Wilk test. Statistical analysis of nonparametric data was performed by Wilcoxon’s test (1-tailed), and statistical analysis of parametric data was performed by paired Student’s t test (1-tailed). Data are plotted as median with interquartile range for nonparametric data and mean ± SEM for parametric data.