Abstract
The complexity of asthma is underscored by the number of cell types and mediators implicated in the pathogenesis of this heterogeneous syndrome. Type 2 CD4+ T-cells (Th2) and more recently, type 2 innate lymphoid cells dominate current descriptions of asthma pathogenesis. However, another important source of these type 2 cytokines, especially interleukin (IL)-5 and IL-13, are CD8+ T-cells, which are increasingly proposed to play an important role in asthma pathogenesis, because they are abundant and are comparatively insensitive to corticosteroids. Many common triggers of asthma exacerbations are mediated via corticosteroid-resistant pathways involving neutrophils and CD8+ T-cells. Extensive murine data reveal the plasticity of CD8+ T-cells and their capacity to enhance airway inflammation and airway dysfunction. In humans, Tc2 cells are predominant in fatal asthma, while in stable state, severe eosinophilic asthma is associated with greater numbers of Tc2 than Th2 cells in blood, bronchoalveolar lavage fluid and bronchial biopsies. Tc2 cells strongly express CRTH2, the receptor for prostaglandin D2, the cysteinyl leukotriene receptor 1 and the leukotriene B4 receptor. When activated, these elicit Tc2 cell chemotaxis and production of chemokines and type 2 and other cytokines, resulting directly or indirectly in eosinophil recruitment and survival. These factors position CD8+ Tc2 cells as important and underappreciated effector cells contributing to asthma pathogenesis. Here, we review recent advances and new insights in understanding the pro-asthmatic functions of CD8+ T-cells in eosinophilic asthma, especially corticosteroid-resistant asthma, and the molecular mechanisms underlying their pathologic effector function.
Abstract
Alongside Th2 and ILC2 cells, CD8+ T-cells are a cellular source of type 2 cytokines. We review recent findings and insights into the pathologic effector functions of type 2 CD8+ T-cells in eosinophilic asthma, especially steroid-resistant disease. http://bit.ly/2KbVGL2
Footnotes
Submitted article, peer reviewed.
Author contributions: T.S.C. Hinks, R.D. Hoyle and E.W. Gelfand jointly conceived the article, conducted the literature review and drafted the manuscript. All authors approved the final manuscript.
Conflict of interest: T.S.C. Hinks reports grants from The Wellcome Trust and The Guardians of the Beit Fellowship, during the conduct of the study; and reports personal fees from AstraZeneca, TEVA, and Peer Voice, outside the submitted work.
Conflict of interest: R.D. Hoyle has nothing to disclose.
Conflict of interest: E.W. Gelfand has nothing to disclose.
Support statement: This work was supported by grants from the Wellcome Trust (104553/z/14/z, 211050/Z/18/z) and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) (to T.S.C. Hinks), the Medical Research Council (UK) (to R.D. Hoyle) and grants HL-36577 and AI-77609 from the National Institutes of Health (to E.W. Gelfand). The views expressed are those of the authors and not those of the NHS, NIHR or NIH. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received July 26, 2019.
- Accepted July 26, 2019.
- Copyright ©ERS 2019.
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.