Alterations in dendritic cells of the aged

A major health concern world‐wide is the increased morbidity and mortality among the elderly due to infectious diseases. Although many studies attribute this increase in incidence to reduced responsiveness and increased functional dysregulation in T lymphocytes of the aged, alterations in the microenvironment in which T cells are stimulated may further contribute to this finding. We found that T cells from young donors that have been transferred to aged hosts and immunized with influenza virus, respond with a delayed onset of division and activation, reduced expansion and differentiation, and diminished migration to the T cell areas of secondary lymphoid organs. Furthermore, dendritic cells (DCs) in aged mice did not significantly upregulate the antigen‐recognition receptor, CD205, migrate to the T cell areas of the spleen and mediastinal lymph nodes, nor express CCR7 upon immunization. Although DCs from the spleens of young mice were capable of restoring deficiencies in CD8 T cell division and migration, DCs from aged donors were not. Upon immunization of aged mice, neither CD8α DC migration nor CCL19 or CCL21 production were enhanced. Altogether, these findings demonstrate that upon immunization DC migration and the production of chemokines that regulate DC and T cell trafficking into lymphoid organs are profoundly reduced thereby further contributing to the immune dysfunction observed in the aged. This work was supported by NIH R01 AG026727.