| Description |
Dendritic cells (DCs) represent the most efficient antigen-presenting cells to initiate primary T cell responses. It is now also appreciated that DCs, through direct cell-cell contacts or as a result of the activities of secreted cytokines, serve to regulate the nature of T cell responses (e.g., Thl or Th2). The present studies demonstrate that CDllc^ bone marrow derived DCs (BMDCS) from aged donors exhibit a phenotype that suggests a more activated basal state of maturation than found with CDllc^ BMDCs derived from young donors. In vitro, compared to BMDCs derived from young donors, BMDCs derived from aged donors exhibit a decreased capacity to capture antigen, but increased abilities to activate peptide-specific T cells following peptide pulsing. These same DC populations, however, appear to display a compromised ability to process native protein antigen and to regulate T cell responses. In vivo, using an injected polystyrene microsphere model, aged mice were found to have higher percentage of Bead^CDl Ic^ cells migrated into the draining lymph nodes after receiving the phagocytic maturation-inducing stimulus. However, fewer microspheres were found in DCs in the draining lymph nodes of aged mice than in DCs of young mice. In vitro, excesses in oxidative stress and exposure to IL-6 can impair the abilities of BMDCs derived from young donors to process and present protein antigen. The mechanisms responsible for this appear different from that exhibited by BMDCs derived from aged donors. Although the molecular mechanisms responsible for impairing the functions of DCs with aging are presently unclear, these studies suggest that some of the age-associated immune dysfunctions may be due to changes in DC functions, resulting in compromised abilities by DCs to initiate and regulate T cell responses. |
