Immunosenescence of macrophages: reduced MHC class II gene expression

In order to determine the effect of aging on macrophages, we produced bone marrow-derived macrophages in vitro from young and aged mice. We analyzed the effect of aging on the genomic expression of macrophages in these conditions, without the influence of other cell types that may be affected by aging. Macrophages from young and aged mice were present in similar numbers and showed an identical degree of differentiation, cell size, DNA content and cell surface markers. After incubation with interferon-gamma (IFN-γ), the expression at the cell surface of the MHC class II gene IA complex product and the levels of intracellular IAβ protein and mRNA were lower in aged macrophages. Moreover, the transcription of IAβ gene was impaired in aged macrophages. The amount of transcription factors that bound to the W and X boxes, but not to the Y box of the IAβ promoter gene were lower in aged macrophages. Similar levels of CIITA mRNA were found after IFN-γ treatment of both young and aged macrophages. This shows that neither the initial cascade that starts after the interaction of IFN-γ with the receptor, nor the second signals involved in the expression of CIITA, are impaired in aged macrophages. These data could explain, at least in part, the impaired immune response associated to senescence.