The effect of B2 agonists on the immune function

Abstract

This project investigated the effect of β2-adrenergic receptor (β2-AR) stimulation on the function of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells in vitro. Catecholamines have been previously shown to increase efflux of these cells into the blood, but the effects on cell function are unclear. In this thesis three aspects of function have been addressed. The results of the studies presented in this thesis showed that: (1) β2-adrenergic stimulation by salmeterol reduced the percentage of IFN-γ producing CD4+ and CD8+ T cells activated by Staphylococcus Aureus enterotoxin type B (SEB) superantigen, cytomegalovirus lysate (CMV) or CMV pp65 (pp65) recombinant protein. (2) salmeterol, at high concentrations, increased rolling behaviour and decreased stationary behaviour of peripheral blood lymphocytes (PBLs) on human microvascular cell line (HMEC-1) and on vascular cell adhesion molecule-1 (VCAM-1), in both flow and static assays. (3) adrenergic stimulation impaired the activation and cytotoxic function of CD8+ T and NK cells, as indicated by lower expression of CD107a (a marker of CD8+ T and NK cell activation and function) following incubation of peripheral blood mononuclear cells (PBMCs) with human erythromyeloblastoid leukemia (K562) cell line or MHC class I chain-related gene A (MICA*009) transfected Chinese hamster ovary cells (T-CHO) was analysed. The results presented in this thesis showed that adrenergic stimulation influences a number of cellular functions, such as those related to migration, cytokine production and cytotoxic function. Together the above studies may contribute to our understanding about how stress affects the ability of the cytotoxic cells