Digital illustration of immune cells interacting with allergens, highlighting TH2A cells.

Cracking the Allergy Code: How Scientists are Unlocking a New Understanding of TH2 Cells

Rhea Morgan in Health & Wellness December 2025 • 4 min read.

"Groundbreaking research identifies a unique subpopulation of T helper 2 cells (TH2A) linked to allergic disorders, offering potential for better diagnostics and targeted therapies."

Allergies affect millions worldwide, turning everyday substances into triggers for a cascade of uncomfortable and sometimes dangerous reactions. For years, scientists have understood that Type 2 helper T cells, or TH2 cells, play a central role in orchestrating these allergic responses. However, the complexity of TH2 cells has been a roadblock in developing truly effective treatments and diagnostic tools.

Traditional approaches have struggled to differentiate between TH2 cells that cause allergic disease and those that might be harmless or even beneficial. This lack of precision limits the effectiveness of therapies and the ability to monitor a patient's response to treatment.

Now, a groundbreaking study published in Science Translational Medicine sheds light on this problem. Researchers have identified a unique subpopulation of human memory TH2 cells, dubbed TH2A cells, that are specifically associated with allergic disorders. This discovery offers a more refined target for future therapies and opens new avenues for understanding the underlying mechanisms of allergy.

What Makes TH2A Cells Different?

Digital illustration of immune cells interacting with allergens, highlighting TH2A cells.

The researchers, led by Erik Wambre and colleagues at the Benaroya Research Institute, conducted a comprehensive analysis of TH2 cells in individuals with various allergies, including those triggered by food, pollen, pet dander, mold, and dust mites. They discovered that TH2A cells possess a unique set of surface markers that distinguish them from conventional TH2 cells. These markers include:

CRTH2: A chemoattractant receptor that helps guide cells to sites of inflammation.
CD161: A natural killer cell marker, suggesting a potential role in immune regulation.
CD49d: A homing receptor that facilitates cell migration to specific tissues.
CD27¯ and CD45RB¯: Indicate that the cells are terminally differentiated, meaning they are highly specialized and mature.

CRTH2: A chemoattractant receptor that helps guide cells to sites of inflammation. CD161: A natural killer cell marker, suggesting a potential role in immune regulation. CD49d: A homing receptor that facilitates cell migration to specific tissues. CD27¯ and CD45RB¯: Indicate that the cells are terminally differentiated, meaning they are highly specialized and mature.

These markers aren't just labels; they signify functional differences. TH2A cells exhibit distinct functional attributes compared to conventional TH2 cells, producing a different profile of cytokines – the signaling molecules that drive allergic inflammation. Transcriptome analysis further revealed that TH2A cells express higher levels of genes involved in initiating pathogenic responses to allergens.

The Future of Allergy Treatment: Targeting TH2A Cells

The identification of TH2A cells as a key driver of allergic responses has significant implications for future research and treatment strategies. By specifically targeting TH2A cells, scientists may be able to develop more effective therapies with fewer side effects. This could involve strategies to eliminate TH2A cells, block their activity, or redirect their function to promote tolerance rather than allergy.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1126/scitranslmed.aam9171, Alternate LINK

Title: A Phenotypically And Functionally Distinct Human T _H 2 Cell Subpopulation Is Associated With Allergic Disorders

Subject: General Medicine

Journal: Science Translational Medicine

Publisher: American Association for the Advancement of Science (AAAS)

Authors: Erik Wambre, Veronique Bajzik, Jonathan H. Delong, Kimberly O’Brien, Quynh-Anh Nguyen, Cate Speake, Vivian H. Gersuk, Hannah A. Deberg, Elizabeth Whalen, Chester Ni, Mary Farrington, David Jeong, David Robinson, Peter S. Linsley, Brian P. Vickery, William W. Kwok

Published: 2017-08-02

Everything You Need To Know

What are TH2 cells, and why are they important in understanding allergies?

TH2 cells, or Type 2 helper T cells, are a type of immune cell that plays a central role in orchestrating allergic responses. They are important because they release signaling molecules (cytokines) that drive allergic inflammation, turning everyday substances into allergy triggers. Understanding their behavior is crucial for developing effective treatments for allergies.

What are TH2A cells, and how do they differ from conventional TH2 cells?

TH2A cells are a unique subpopulation of human memory TH2 cells specifically associated with allergic disorders. They differ from conventional TH2 cells by possessing a unique set of surface markers: CRTH2, CD161, CD49d, and the absence of CD27 and CD45RB (CD27¯ and CD45RB¯). These markers signify functional differences, including a distinct cytokine production profile and higher expression of genes involved in initiating pathogenic responses to allergens. TH2A cells are considered terminally differentiated.

How might the discovery of TH2A cells impact the future of allergy treatment?

The identification of TH2A cells as key drivers of allergic responses allows scientists to target these cells specifically. This could lead to the development of more effective therapies with potentially fewer side effects. Strategies may include eliminating TH2A cells, blocking their activity, or redirecting their function to promote tolerance rather than allergy. Precise targeting of TH2A cells should enable better monitoring of a patient's response to treatment.

What role do surface markers like CRTH2, CD161, and CD49d play in the function of TH2A cells?

The surface markers found on TH2A cells each contribute to their specific function. CRTH2 is a chemoattractant receptor that guides the cells to sites of inflammation. CD161 is a natural killer cell marker, suggesting a potential role in immune regulation. CD49d is a homing receptor that facilitates cell migration to specific tissues. The absence of CD27 and CD45RB indicates that TH2A cells are terminally differentiated, meaning they are highly specialized and mature. These markers are not just labels; they signify functional differences in TH2A cells compared to conventional TH2 cells.

The study mentions transcriptome analysis of TH2A cells. What does this reveal about their role in allergic responses, and why is it important?

Transcriptome analysis of TH2A cells revealed that they express higher levels of genes involved in initiating pathogenic responses to allergens. This is important because it confirms that TH2A cells are a key driver of allergic inflammation. Transcriptome analysis allows scientists to understand the set of genes and RNA transcripts expressed within the TH2A cells. A process known as RNA sequencing measures the quantity of RNA present in the cell, allowing scientists to determine which RNA and genes are specifically related to allergic response.