Functions of T cells in asthma: more than just TH2 cells

Subjects

Key Points

  • Several T cell subsets are involved in the development of the diseases we call asthma, not just T helper 2 (TH2) cells.

  • Emerging data describe the existence of innate immune cells that are capable of producing TH2-type cytokines and promoting TH2-type responses, even in the absence of T cells.

  • T cells are not always lineage committed but show plasticity within the local cytokine environment.

  • Environmental influences such as age, gender, obesity, infection history, atopic status, allergen exposure levels, antibiotic use, exposure to pollution, and nutrition (for example, levels of vitamin A, vitamin D and vitamin E and hormone exposure) contribute to the heterogeneity of clinical disease.

  • Cluster analysis shows distinct clinical phenotypes of asthma; these data are useful for designing therapeutic approaches that are tailored towards specific asthma symptoms.

Abstract

Asthma has been considered a T helper 2 (TH2) cell-associated inflammatory disease, and TH2-type cytokines, such as interleukin-4 (IL-4), IL-5 and IL-13, are thought to drive the disease pathology in patients. Although atopic asthma has a substantial TH2 cell component, the disease is notoriously heterogeneous, and recent evidence has suggested that other T cells also contribute to the development of asthma. Here, we discuss the roles of different T cell subsets in the allergic lung, consider how each subset can contribute to the development of allergic pathology and evaluate how we might manipulate these cells for new asthma therapies.

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Figure 1: T cells involved in the induction of the allergic phenotype.
Figure 2: Alternative pathway to a TH2-type response in the airways.
Figure 3: T cell subset signatures are affected by a variety of genetic and environmental influences.

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Acknowledgements

The authors acknowledge R. Coffman for his critical reading and input, A. Calver for his contribution to the supplementary information and K. Alexander for her help with the manuscript.

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Correspondence to Clare M. Lloyd.

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Edith M. Hessel has been employed by GlaxoSmithKline since July 2009.

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Glossary

Airway hyperresponsiveness

(AHR). A hyperreactivity of the airways, initiated by exposure to a defined stimulus that is usually tolerated by normal individuals; it causes bronchoconstriction and inflammatory-cell infiltration in allergic individuals. This is a defining physiological characteristic of asthma.

Forced expiratory volume in 1 second

(FEV1). A primary indicator of lung function.

Hygiene hypothesis

This hypothesis originally proposed that the increased incidence of atopic diseases in westernized countries was a consequence of living in an overly clean environment, resulting in an under-stimulated immune system that responded inappropriately to harmless antigens. More recently it has been proposed that an absence of exposure to pathogens, in particular helminths, may predispose to both increased allergy and autoimmune disease.

β2-agonist

A class of medication aimed at dilating the airways by the agonism of the β-adrenoreceptor pathway.

Allergen-specific immunotherapy

Allergen immunotherapy was introduced in the early 1900s. In general, it involves subcutaneous injection of increasing doses of specific allergen into the patient. This is carried out under carefully controlled clinical conditions because of the potential for life-threatening adverse reactions. On average, it results in 50% reduction of clinical symptoms and medication usage, and it also results in beneficial modifications of the patient's immune response to allergen. Following the initial course of injections (either conventional or rushed), patients receive maintenance injections (less frequently) of allergen for optimal clinical benefit.

MicroRNA

Small, non-coding RNA molecules that regulate the expression of several genes by binding to the 3′ untranslated regions of specific mRNAs.

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Lloyd, C., Hessel, E. Functions of T cells in asthma: more than just TH2 cells. Nat Rev Immunol 10, 838–848 (2010). https://doi.org/10.1038/nri2870

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