T-cell responses in asthma exacerbations

Abstract

Objective: Asthma is a chronic lung disease comprising multiple endotypes and characterized by periodic exacerbations. A diverse array of T cells has been found to contribute to all endotypes of asthma in pathogenic and regulatory roles. Here, we review the contributions of CD4+, CD8+, and unconventional T cells in allergic and nonallergic asthma.

Data sources: Review of published literature pertaining to conventional and unconventional T-cell types in asthma.

Study selections: Recent peer-reviewed articles pertaining to T cells in asthma, with additional peer-reviewed studies for context.

Results: Much research in asthma has focused on the roles of CD4+ T_H cells. Roles for T_H2 cells in promoting allergic asthma pathogenesis have been well-described, and the recent description of pathogenic T_H2A cells provides additional insight into these responses. Other T_H types, notably T_H1 and T_H17, have been linked to neutrophilic and steroid-resistant asthma phenotypes. Beyond CD4+ T cells, CD8+ Tc2 cells are also strongly associated with allergic asthma. An emerging area for study is unconventional T-cell types, including γδT, invariant natural killer T, and mucosal-associated invariant T cells. Although data in asthma remain limited for these cells, their ability to bridge innate and adaptive responses likely makes them key players in asthma. A number of asthma therapies target T-cell responses, and, although data are limited, they seem to modulate T-cell populations.

Conclusion: Given the diversity and heterogeneity of asthma and T-cell responses, there remain many rich avenues for research to better understand the pathogenesis of asthma. Despite the breadth of T cells in asthma, approved therapeutics remain limited to T_H2 networks.

Figure 1.. Differentiation and therapeutic targeting of Th cells involved in asthma pathogenesis.

(A) Overview of the differentiation of Th subsets, production of key effector cytokines, and their downstream effects. (B) Therapeutic targeting of T-cell responses, denoted numerically. Treatments approved for use in asthma are denoted in bold font, with faded downstream immune pathways; treatments that are no longer in development and/or that lacked efficacy in clinical trials for asthma are struck through; treatments requiring further investigation are depicted in normal font. Figure created using BioRender.com. AHR, airway hyperreactivity; DC, dendritic cell; Eos., eosinophil; Neut., neutrophil, Th, T helper