Figures
- FIGURE 1
Under the influence of interleukin-(IL)-4, type 2 CD8+ (Tc2) cells differentiate from naïve CD8+ T-cells or arise by transcriptional reprograming of Tc1 cells. Tc2 cells highly express chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), a receptor for prostaglandin D2 (PGD2). In addition, Tc2 cells express the cysteinyl leukotriene receptor 1 (CysLT1) and leukotriene B4 receptor (BLT-1). Inflammatory stimuli, such as cross-linking of immunoglobulin (Ig)E on mast cells, leads to production of eicosanoids. Through CRTH2, PGD2 elicits Tc2 cell chemotaxis, activation and production of chemokines, type 2 cytokines and other cytokines, resulting directly or indirectly in eosinophil recruitment and survival. In turn, airway eosinophilia is associated with airway remodelling and exacerbations. ATF2: activating transcription factor-2; CCL: C-C motif chemokine ligand; GM-CSF: granulocyte–macrophage colony-stimulating factor; LT: leukotriene; MKP: mitogen-activated protein kinase phosphatase; Th2 cells: type 2 CD4+ T-cells; TNF: tumour necrosis factor.
- FIGURE 2
Tc2 cells are enriched in eosinophilic asthma. a) Frequencies of CD3+CD8+CRTH2+ Tc2 and CD3+CD4+CRTH2+ Th2 cells in CD4+ or CD8+ T-cells in total peripheral blood leucocytes compared between healthy controls and severe asthma patient groups (eosinophilic and non-eosinophilic) in a cohort from Oxford, UK by flow cytometry. b,c) Tc2 cells are increased in lung in eosinophilic asthma in a cohort from Southampton, UK. Frequencies of CD3+CD8+IL-13+ and CD3+CD4+IL-13+ T-cells in b) bronchial biopsy and c) bronchoalveolar lavage (BAL) compared between healthy controls and asthma groups (eosinophilic and non-eosinophilic) by intracellular cytokine staining. *: p<0.05, ***: p<0.001. Reproduced and modified from [88] with permission.
Tables
- TABLE 1
Common triggers for asthma exacerbations are mediated by different pathways, frequently involving steroid-unresponsive neutrophils and CD8 cells
Allergen exposure Viral infection Ozone/diesel exhaust Cigarette smoke Bacterial infection Predominant pathway Th2 cells, IgE Th1 cells, leukotrienes Th1 cells, leukotrienes Th1 cells, leukotrienes Th17 cells, IL-1β, IL-6, TNF Predominant effector cells Eosinophils, Mast-cells, CD4 T-cells Neutrophils, CD8 T-cells Neutrophils, CD8 T-cells Neutrophils, CD8 T-cells Neutrophils Steroid responsiveness High Low Low Low Low Th1/2 cells: type 1/2 CD4+ T-cells; IL: interleukin; TNF: tumour necrosis factor.
