Age-associated shift in rat dendritic cell T-helper polarizing capacity

Abstract

Almost all cellular components of innate and adaptive immunity undergo age-related remodeling. The findings on age-related changes in human and mouse dendritic cells (DCs) are conflicting, whereas there is no data on the influence of aging on rat DCs. In attempt to fill this gap, freshly isolated splenic conventional OX62+ DCs from 3- (young) and 26-month-old (aged) Albino Oxford rats were examined for subset composition, cell surface expression of activation markers (CD80, CD86 and CD40 and MHC II molecules) and endocytic capacity using flow cytometric analysis (FCA). In addition, splenic OX62+ DCs isolated from rats of both ages were cultured in the presence or in the absence of LPS. These cells were examined for the activation marker and TNF-α, IL-6, IL-12, IL-23, TGF-β1, IL-10 expression using FCA, and RT-PCR and ELISA, respectively. Moreover, the allostimulatory capacity of OX62+ DCs and allogeneic CD4+ T cell cytokine (IFN-γ, IL-4 and IL-17) production in MLR was quantified using FCA and ELISA, respectively. It was found that aging: i) in OX62+ DCs population leads to a shift in CD4+:CD4- cell ratio towards CD4- cells and ii) influences OX62+ DCs maturation capacity (judging by activation marker expression and efficiency of endocytosis) by affecting action of intrinsic (TNF- α and IL-10) and extrinsic regulatory factor expression. Furthermore, in LPS-matured OX62+ DCs from aged rats TNF-α, IL-12, IL-23 and IL-6 expression was increased, while IL-10 expression was diminished. Moreover, in MLR, OX62+ DCs from aged rats exhibited enhanced Th1/Th17 driving force and diminished allostimulatory capacity.