Aging affects AO rat splenic conventional dendritic cell subset composition, cytokine synthesis and T-helper polarizing capacity

Abstract

It is well-established that almost all cellular components of innate and adaptive immunity undergo age-related remodelling. The findings on age-related changes in both human and mouse dendritic cells (DCs) are conflicting, whereas there are no data on the influence of aging on rat DCs. In an attempt to fill this gap, freshly isolated splenic DCs expressing CD103 (alpha(OX-62) integrin), a DC specific marker recognized by MRC OX62 monoclonal antibody, from 3- (young) and 26-month-old (aged) Albino Oxford rats were examined for subset composition, expression of activation/differentiation markers (CD80, CD86 and CD40 and MHC II molecules) and endocytic capacity using flow cytometric analysis (FCA). In addition, splenic OX62+ DCs cultured in the presence or absence of LPS were analysed for the activation marker and TNF-alpha, IL-6, IL-12, IL-23, TGF-beta 1, IL-10 expression using FCA, RT-PCR and ELISA, respectively. Moreover, the allostimulatory capacity of OX62+ DCs and IFN-gamma, IL-4 and IL-17 production by CD4+ T cells in mixed leukocyte reaction was quantified using FCA and ELISA, respectively. It was found that aging: i) shifts the CD4+:CD4- subset ratio in the OX62+ DCs population towards the CD4- subset and ii) influences DCs maturation (judging by activation marker expression and efficiency of endocytosis) by affecting the expression of intrinsic (TNF-alpha and IL-10) and extrinsic maturation regulators. Furthermore, in LPS-matured OX62+ DCs from aged rats expression of TNF-alpha, IL-12, IL-23 and IL-6 was increased, whereas that of IL-10 was diminished compared with the corresponding cells from young rats. Moreover, in MLR, OX62+ DCs from aged rats exhibited enhanced Th1/Th17 driving force and diminished allostimulatory capacity compared with those from young rats.