Identification of a T follicular helper cell subset that drives anaphylactic IgE

• Published in: Science (American Association for the Advancement of Science) Vol. 365; no. 6456
• Main Authors: Gowthaman, Uthaman, Chen, Jennifer S, Zhang, Biyan, Flynn, William F, Lu, Yisi, Song, Wenzhi, Joseph, Julie, Gertie, Jake A, Xu, Lan, Collet, Magalie A, Grassmann, Jessica D S, Simoneau, Tregony, Chiang, David, Berin, M Cecilia, Craft, Joseph E, Weinstein, Jason S, Williams, Adam, Eisenbarth, Stephanie C
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 30-08-2019
• Subjects: Ablation; Adolescent; Affinity; Allergens; Allergic diseases; Allergies; Allergy; Anaphylaxis; Anaphylaxis - immunology; Animals; Antibodies; Child; Crosslinking; Cytokines; Feedback (Response); Food; GATA3 Transcription Factor - metabolism; Gene sequencing; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - metabolism; Helper cells; Humans; Immunization; Immunoglobulin E; Immunoglobulin E - immunology; Immunoglobulins; Infections; Interleukin-13 - genetics; Interleukin-13 - metabolism; Interleukins; Lymph nodes; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Parasites; Peanuts; Population; Proto-Oncogene Proteins c-bcl-6 - metabolism; Receptors; Switching; T-Lymphocytes, Helper-Inducer - immunology; Worms
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aaw6433

Cross-linking of high-affinity immunoglobulin E (IgE) results in the life-threatening allergic reaction anaphylaxis. Yet the cellular mechanisms that induce B cells to produce IgE in response to allergens remain poorly understood. T follicular helper (T
) cells direct the affinity and isotype of antibodies produced by B cells. Although T
cell-derived interleukin-4 (IL-4) is necessary for IgE production, it is not sufficient. We report a rare population of IL-13-producing T
cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These "T
13" cells have an unusual cytokine profile (IL-13
IL-4
IL-5
IL-21
) and coexpress the transcription factors BCL6 and GATA3. T
13 cells are required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking T
13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.