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.