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Immune tolerance of food is mediated by layers of CD4 + T cell dysfunction.
- Source :
-
Nature [Nature] 2022 Jul; Vol. 607 (7920), pp. 762-768. Date of Electronic Publication: 2022 Jul 06. - Publication Year :
- 2022
-
Abstract
- Gastrointestinal health depends on the adaptive immune system tolerating the foreign proteins in food <superscript>1,2</superscript> . This tolerance is paradoxical because the immune system normally attacks foreign substances by generating inflammation. Here we addressed this conundrum by using a sensitive cell enrichment method to show that polyclonal CD4 <superscript>+</superscript> T cells responded to food peptides, including a natural one from gliadin, by proliferating weakly in secondary lymphoid organs of the gut-liver axis owing to the action of regulatory T cells. A few food-specific T cells then differentiated into T follicular helper cells that promoted a weak antibody response. Most cells in the expanded population, however, lacked canonical T helper lineage markers and fell into five subsets dominated by naive-like or T follicular helper-like anergic cells with limited capacity to form inflammatory T helper 1 cells. Eventually, many of the T helper lineage-negative cells became regulatory T cells themselves through an interleukin-2-dependent mechanism. Our results indicate that exposure to food antigens causes cognate CD4 <superscript>+</superscript> naive T cells to form a complex set of noncanonical hyporesponsive T helper cell subsets that lack the inflammatory functions needed to cause gut pathology and yet have the potential to produce regulatory T cells that may suppress it.<br /> (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Subjects :
- Allergens immunology
Antibody Formation
Dietary Proteins immunology
Gastrointestinal Tract cytology
Gastrointestinal Tract immunology
Gliadin immunology
Inflammation
Interleukin-2 immunology
Liver cytology
Liver immunology
Lymphoid Tissue cytology
Lymphoid Tissue immunology
Peptide Fragments immunology
T Follicular Helper Cells cytology
T Follicular Helper Cells immunology
T-Lymphocytes, Regulatory cytology
T-Lymphocytes, Regulatory immunology
Th1 Cells cytology
Th1 Cells immunology
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes immunology
Food
Immune Tolerance immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 607
- Issue :
- 7920
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 35794484
- Full Text :
- https://doi.org/10.1038/s41586-022-04916-6