Aging Aging

Dendritic Cells in Old Age 293had received marrow cells from aged animals than in those mice that had beengrafted with marrow from young mice. This suggests that the frequency of DCprogenitors may be lower in aged mice. Alternatively, the migration of progenitorsfrom the marrow to their target tissues or the homing of progenitorsmay be impaired in aged animals. These possibilities are yet to be clarified.1.3.3. Distribution of DCsLCs, that is, the epidermal variant of DCs, have been studied in some detail,the most obvious question being whether the numbers of LCs change with age.Immunohistochemistry (using monoclonal antibodies [MAbs] against MHC classII) and enzyme histochemistry (using ATPase staining) were generally applied toaddress this issue. Several authors found a decline of LC densities in the epidermiswith age (25–27). The extent of LC reduction was about one third. This wasalso observed with LCs in the oral mucosa: a reduction by 30–60% was reportedin the mouse (28) and a reduction of LC foci and interfocal LCs in the hamstercheek pouch (29). In contrast, a study in the rat reported an unchanged density ofDCs (reactive with MAb OX-6) in the mucosa of the tooth pulp (30). So didanother investigation of the mouse gingiva (31). No detailed studies are availableconcerning age-related changes in numbers and distribution of DCs from sourcesother than the skin (spleen, lymph nodes, thymus).1.3.4. Function of DCsThe experiments reviewed here are too few in number to allow well-foundedconclusions. Important questions have not yet been addressed. It has not beendissected which component of DC function is reduced with age. The three broadfunctions of DCs as delineated by Steinman (1; see Subheading 1.1.) are separatedfrom each other in space and time. They are down- and up-regulated inthe course of the maturation process. Therefore, the experiments discussedbelow also imply an analysis of the maturation process in relation to age.1.3.5. T-Cell Stimulatory Properties of Murine DCsAntigen processing may be affected by age. The observations by Haruna etal. (24) that the impaired T-cell stimulatory function of DCs did not correlatewith the expression of such crucial molecules as the costimulators CD80 andCD86 leads one to speculate that perhaps the generation of immunogenic MHCclass II/peptide complexes may be diminished as well. This aspect of immunogenicitycould easily be studied by means of peptide-specific T-cell hybridomas(32). The development of T-cell-sensitizing capacity of DCs with age isanother important point. Early work showed an increase of the immunostimulatorycapacity of spleen DCs from C57BL/6 mice in the syngeneic mixedleukocyte reaction, but not in the allogeneic mixed leukocyte reaction or in the