Although many studies have shown that pulmonary surfactant protein (SP)-A functions in innate immunity, fewer studies have addressed its role in adaptive immunity and allergic hypersensitivity. We hypothesized that SP-A modulates the phenotype and prevalence of dendritic cells (DCs) and CD4+ T cells to inhibit Th2-associated inflammatory indices associated with allergen-induced inflammation. In an OVA model of allergic hypersensitivity, SP-A-/- mice had greater eosinophilia, Th2-associated cytokine levels, and IgE levels compared with wild-type counterparts. Although both OVA-exposed groups had similar proportions of CD86+ DCs and Foxp3+ T regulatory cells, the SP-A-/- mice had elevated proportions of CD4+ activated and effector memory T cells in their lungs compared with wild-type mice. Ex vivo recall stimulation of CD4+ T cell pools demonstrated that cells from the SP-A-/- OVA mice had the greatest proliferative and IL-4 - producing capacity, and this capability was attenuated with exogenous SP-A treatment. Additionally, tracking proliferation in vivo demonstrated that CD4+ activated and effector memory T cells expanded to the greatest extent in the lungs of SP-A-/- OVA mice. Taken together, our data suggested that SP-A influences the prevalence, types, and functions of CD4 + T cells in the lungs during allergic inflammation and that SP deficiency modifies the severity of inflammation in allergic hypersensitivity conditions like asthma.
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