Effect of Aging on Bone Marrow-Derived Murine CD11c+CD4-CD8 - Dendritic Cell Function

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Abstract
Dendritic cells (DCs) are actively used as cellular adjuvant in cancer immunotherapy. However, although DC immunotherapies primarily target the elderly population, little is known about the effect of aging on DC functions. Here, we compared the T-cell stimulation, cytokine production, and tumor surveillance functions of bone marrow-derived CD11c+CD4−CD8α− DCs of old and young C57BL/6 mice. Old immature bone marrow-derived CD4−CD8α− DCs (imDCs) were 4 times less effective than were young DCs in stimulating syngeneic CD4+ T-cell proliferation. Old imDCs also have decreased DC-specific/intracellular adhesion molecule type 3-grabbing, nonintegrin (DC-SIGN) expression compared to young DCs. Interestingly, mice treated with the ovalbumin peptide-pulsed young DCs exhibited significantly greater tumor regression than with ovalbumin peptide-pulsed old DCs. Old terminally differentiated bone marrow-derived DCs (tDC) also have increased interleukin-10, but decreased interleukin-6 and tumor necrosis factor-α production. Taken together, these results have important implications in the clinical application of DC-based tumor immunotherapy in elderly persons.