Congresos y reuniones científicas
Título:
AGING IMPAIRS CD8+ T CELL TRIGGERING BY DENDRITIC CELLS STIMULATED THROUGH TLR7
Autor/es:
ZACCA, E; CRESPO, MI; ACLAND,R; NUÑEZ, N; MACCIONI, M; MALETTO, B; PISTORESI, MC; MORÓN, G
Reunión:
Congreso; LXI Reunión de la Sociedad Argentina de Inmunología.; 2013
Institución organizadora:
Sociedad Argentina de Inmunologia
Resumen:
Cumulative evidence indicates that aging is characterized by an altered function of the immune system. Age-related changes in the innate and the adaptive immune responses have been well established with focus on the adaptive immunity. The role of Dendritic Cells (DCs) in age-related immune function is not completely understood. Our previous findings show, using polyuridylic acid (polyU), a TLR7 ligand, and ovalbumin (OVA) as an antigen (Ag) model, that DCs from old mice have impaired ability to crosspresent Ag and thus, to generate efficient effector CD8+ T cell responses. To test the mechanism involved in this process we compared Ag degradation in DCs from 6- to 8-week old mice (young) and from 20- to 22-month old mice (old). We found that DCs from old mice have a significantly lower ability to degrade OVA than DCs from young mice (p < 0.001), clearly demonstrating that DCs from old mice have a diminished ability to process exogenous Ag. Remarkably, we have previously reported that DCs from old mice show an impaired maturation capacity upon TLR7 stimulation. So we test whether this lower capacity of DCs from old mice to maturate could be due, at least in part, to a reduced expression of TLRs. By real time quantitative PCR we observed a reduced expression of mRNA TLR7 in all spleen DCs subsets from old mice compared to their young counterparts (p < 0.05). We also studied the intracellular signaling pathway of TLR7. Using Western Blot we found an altered IkB-a phosphorylation pattern upon TLR7 stimulation in DCs from old mice compared to their young counterparts. All together this results indicate that impaired ability to generate efficient effector CD8+ T cell responses could be related to age-associated changes in Ag processing by DCs and a by a dysregulation in DC activation. Our results provide evidence that immunosenescence in DCs represents one of the factors contributing to the decline in immune function with age.