Epinephrine autoinjectors won’t be obsolete soon, if ever. But they might find allies in their mission, the tamping down of life-threatening allergic reactions. A particularly extreme allergic reaction, anaphylaxis, appears to involve a rare, distinctive immune cell, the T follicular helper cell 13, or Tfh13.

According to scientists from Yale University and the Jackson Laboratory for Genomic Medicine, Tfh13 is responsible for directing antibody-producing B cells to create high-affinity immunoglobulin E (IgE) antibodies.

The production of high levels of high-affinity IgE antibodies, which bind strongly to allergens to spur allergic reactions, has been linked to allergies and anaphylaxis. In fact, IgE-mediated anaphylaxis happens to be the prototypical anaphylaxis. Consequently, therapies that suppress IgE—by targeting Tfh13 cells—might prevent the onset of anaphylaxis when an allergic person is exposed to an antigen.

The Yale/Jackson team presented their findings August 1 in the journal Science, in an article titled, “Identification of a T follicular helper cell subset that drives anaphylactic IgE.” The article describes how the scientists discovered Tfh13 cells by using laboratory mice bred to have a rare genetic immune disease called DOCK8 immunodeficiency syndrome.

Patients with mutations in DOCK8 are immunodeficient, but paradoxically present with hyper-IgE syndrome and associated food allergies and asthma. DOCK8 immunodeficiency syndrome eventually causes patients to suffer recurrent viral infections of the skin and respiratory system—as well as severe allergies and asthma.

The investigators noted that mice with a DOCK8 deficiency had novel T follicular helper cells, not found in normal mice, that produced a unique combination of chemical messengers called cytokines.

“We report a rare population of IL-13-producing Tfh cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity,” the article’s authors wrote. “These ‘Tfh13’ cells have an unusual cytokine profile (IL-13hiIL-4hiIL-5hiIL-21lo) and co-express BCL6 and GATA3. They were required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis.”

The scientists took mice with normal immune systems and sensitized them with respiratory and food allergens to induce severe allergic reactions leading to anaphylaxis. While non-allergic mice lacked Tfh13 cells, allergic mice had both Tfh13 cells and high-affinity IgE.

“Conditional deletion of Tfh13 cells or IL-13 in Tfh cells abrogated the generation of high-affinity anaphylactic IgE to allergens,” the article’s authors indicated. That is, through genetic manipulation, the scientists prevented Tfh13 cell development in mice and found that the animals did not make anaphylactic IgE to allergens.

To transfer this insight to humans, the scientists compared blood samples from people with peanut or respiratory allergies to those of non-allergic volunteers and found that individuals with allergies and the associated IgE had elevated levels of Tfh13 cells.

“Our study defines the role of Tfh13 cells in eliciting anaphylactic IgE to allergens, identifying specific molecular targets that could be leveraged diagnostically and therapeutically for allergies,” the article’s authors concluded. “Identification of Tfh13 cells answers the long-standing question of how, under rare circumstances, anaphylaxis-inducing IgE is produced by high-affinity B cells.”

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