Aging Aging

294 Grubeck-Loebenstein, Saurwein-Teissl, and Romanipolyclonal response to concanavalin A (33). A recent and detailed study utilizeda substrain of SAMP1 mice. The authors investigated the allogeneic mixedleukocyte reaction as a measure for the capacity of DCs to stimulate restingT-cells. Spleen DCs from aged SAMP1 mice stimulated less well in this assaythan DCs derived from age-matched BALB/c mice or from young SAMP1 mice(24). These changes correlated with the expression of MHC class II and adhesionmolecules (CD54/ICAM–1) but, interestingly, not with the expression ofcostimulator molecules (CD80/B7–1 and CD86/B7–2) on DCs. Clearly, morestudies are needed to construct a conclusive picture. Other factors contributingto the sensitizing potential of murine DCs have not been analyzed to date.Examples are the capacity to cluster T-cells in vitro (34) and in vivo (35) or theability to secrete IL-12 (36).1.3.6. Migratory FunctionMigration of DCs from the sites of antigen uptake (e.g. the skin) to theregional lymphatic organs is essential for the successful generation of animmune response. DCs typically migrate through lymphatic vessels. Recently,a novel pathway of DC migration was identified, namely a transition of DCsfrom the blood into the lymph in the liver (37). It would be interesting to knowwhether migration is impaired in aged mice. Indirect evidence for this stemsfrom contact hypersensitivity experiments. The induction of contact hypersensitivitycorrelates with an efflux of LCs from the epidermis and their entryinto dermal lymphatics (38). Sprecher et al. (25) noted that the capacity of LCsto transport antigen (the contact sensitizer rhodamine) from the skin to thedraining lymph nodes was not impaired in old mice. The clinical outcome ofthis antigen transport, that is contact hypersensitivity, was found to be reducedin one study with aged mice (39), and more variable but not reduced in anotherstudy (27). No consensus has thus yet been reached regarding DC migrationduring aging. Skin organ cultures (38,40) may be a suitable experimental systemto directly study this issue in more depth.1.4. DCs in Aged Humans1.4.1. Ontogeny and Distribution of DCsOnly limited information is at present available on DCs in aged humans. It istherefore not clear whether the frequency of DCs progenitors decreases duringthe aging process. No studies have ever addressed the question whether thecapacity of the bone marrow to generate DCs changes with age. Early studieshave demonstrated a decreased density and functional activity of LCs in theaged skin (41,42). This may, however, partly be due to UV irradiation, as sig-