The immune system defends against threats using both innate and adaptive mechanisms. A central component of the adaptive response is the T helper cell (Th cell), a type of white blood cell that directs other immune cells to fight specific pathogens. Th cells differentiate into distinct subsets, such as Th1, Th17, and Th2 cells, each specializing in combating different invaders. The Th2 subset specifically manages immune responses against large, extracellular threats and promotes antibody production. Understanding Th2 cell function provides insight into how the body defends itself and how this system can contribute to inflammatory diseases.
Defining Th2 Cells and Their Differentiation
Th2 cells originate from naïve CD4+ T lymphocytes, which circulate before encountering a specific foreign substance. The differentiation of a naïve T cell into a Th2 cell is driven by signals from the surrounding cellular environment. For a T cell to commit to the Th2 lineage, the cytokine Interleukin-4 (IL-4) must be present when the T cell receptor is activated by an antigen.
When IL-4 binds to its receptor, it initiates a signaling cascade that activates the protein Signal Transducer and Activator of Transcription 6 (STAT6). Activated STAT6 moves into the nucleus, triggering the expression of the master transcription factor, GATA3. GATA3 changes the cell’s genetic program, locking in the Th2 identity.
The induction of GATA3 promotes the production of signature Th2 cytokines and actively suppresses the differentiation pathways of other T helper subsets, such as Th1 cells. Once established, the Th2 cell is defined by the unique signaling molecules it produces. These include IL-4, Interleukin-5 (IL-5), and Interleukin-13 (IL-13).
Primary Function: Orchestrating Antibody Responses
The primary function of Th2 cells is to coordinate defense against large, extracellular parasites, such as helminths (parasitic worms). These parasites are too large to be destroyed by individual phagocytic cells like macrophages, requiring a strategy of expulsion and neutralization. Th2 cells achieve this defense by promoting humoral immunity, which involves the production of antibodies.
Th2 cells utilize IL-4 to instruct B lymphocytes (antibody-producing cells) to undergo class switching. This instruction specifically drives B cells to produce Immunoglobulin E (IgE). IgE antibodies are a distinctive feature of the Th2 response, designed to coat the surface of mast cells and basophils, preparing them for rapid action against the parasite.
The other major cytokines produced by Th2 cells recruit and activate additional specialized immune cells. Interleukin-5 (IL-5) is the primary signal for the production, maturation, and recruitment of eosinophils from the bone marrow to the site of infection. Eosinophils release toxic proteins onto the surface of parasites, aiding in their destruction.
Interleukin-13 (IL-13) acts directly on structural cells, particularly in the gastrointestinal tract and airways. IL-13 promotes the increased secretion of mucus by goblet cells and enhances smooth muscle contraction. These mechanical mechanisms physically trap and expel the parasite from the body through coughing, sneezing, or increased gut motility.
Th2 Cell Involvement in Allergic Disease
While the Th2 response protects against parasitic infections, it can become misdirected against harmless environmental substances, leading to allergic disease. This misdirected response is known as Type I Hypersensitivity, where the immune system overreacts to common, non-threatening antigens called allergens (e.g., pollen or dust mites). The core components of the normal anti-parasite response—IgE and mast cells—are central to this pathology.
Initial exposure to an allergen causes Th2 cells to generate allergen-specific IgE antibodies, which bind tightly to receptors on mast cells in a process called sensitization. Upon subsequent exposure, the IgE molecules on the sensitized mast cells cross-link, triggering a rapid release of potent inflammatory mediators, most notably histamine. This degranulation process is responsible for the immediate symptoms of an allergic reaction, including itching, swelling, and bronchoconstriction.
In chronic conditions like asthma, Th2 cytokines contribute to persistent inflammation and tissue damage in the airways. IL-5 drives the recruitment of eosinophils into the lungs, where their prolonged activation damages the respiratory lining. Simultaneously, IL-13 promotes mucus hypersecretion and contributes to airway remodeling, including thickening of the airway walls and increased smooth muscle responsiveness. This combination results in the airflow limitation and hyperresponsiveness characteristic of asthma.