Flt3 Ligand and CpG ODN Abrogate Impaired Antigen Presenting Cell Function by Aged Dendritic Cells

Abstract

The immunodeficiency and increased risk of infection seen in elderly patients may be attributable to an alteration in the immune system. Since dendritic cells (DCs) play a key role for the induction of antigen (Ag)-specific immune responses, we hypothesize that upregulation of aged DCs function by flt3 ligand and CpG ODN abrogate for the induction of Ag-specific adjuvant immune responses. Mononuclear cells were isolated from spleen of BALB/c mice (>24 months of age) and were stained with an array of fluorescence-conjugated mAbs in order to determine the frequencies of DCs by fluorescence activated cell sorter (FACS). The spleen from aged mice contained reduced frequencies CD8⁺ DCs and pDCs. Further, aged splenic DCs showed impaired APC function when compared with DCs from young adult mice. To compensate this age-associated alterations, flt3 ligand (FL) and CpG ODN were employed. When aged splenic DCs were cultured with recombinant (r) FL and CpG ODN, significant proliferative responses were induced, which is essentially identical to that of splenic DCs from young mice. Further, aged mice given nasal OVA plus FL plasmid (pFL) and CpG ODN showed high levels of OVA-specific IgG and IgA Abs in plasma which are comparable to those of young adult mice. Thus, the frequencies of CD8⁺ DCs and plasmacytoid DCs in spleen of aged mice were significantly increased after the immunization with pFL and CpG OND. More importantly, aged splenic DCs expressed increased frequencies of the costimulatory molecules. These results showed that a combination of pFL and CpG ODN treatment was an effective strategy to enhance impaired immunity that is seen in aged mice.