Virus induced airway hyperreactivity in allergen sensitized animals is mediated by immunological memory and is ablated by dexamethasone (55.14)

Abstract

Abstract Common cold viruses are the leading cause of asthma exacerbations. Why people with asthma develop such severe reactions is unclear. We hypothesize that it is not the severity of virus infection but the activation of memory T-cells and eosinophils, which cause the airway hyperreactivity (AHR). We have a model with virus memory T cells in allergen-sensitized guinea pigs (GP). GP are sensitized (i.p.) to ovalbumin (OVA) or not. All receive an inhaled OVA challenge. Some of each group are exposed once to parainfluenza virus (PIV) then, 6 weeks later, re-exposed to either live virus or UV-inactivated virus. Measurements of AHR (histamine i.v.), inflammation (BAL/histology), and T cell memory (BrdU incorporation ex vivo) are measured. Additionally some animals from each group were pre-treated with dexamethasone (DEX) (i.p.) before re-exposure to PIV. Both non-sensitized and OVA-sensitized GPs develop T cell memory to virus based on BrdU incorporation data from lymph node T cells. Unlike non-sensitized GP, OVA-sensitized GP show elevated numbers of eosinophils in the airways, except those pre-treated with DEX. Unlike non-sensitized GP, OVA-sensitized GP develop AHR upon re-exposure to UV-inactivated virus, which is prevented by DEX. GP can develop T cell memory to PIV. Upon re-exposure to PIV antigens, this T cell memory can cause AHR but only sensitized animals, which we believe is mediated by eosinophils. DEX prevents AHR in sensitized animals re-exposed to viral antigens.