AGING IMPAIRS THE ABILITY OF CONVENTIONAL DENDRITIC CELLS TO CROSS-PRIME CD8+ T CELLS UPON STIMULATION WITH A TLR7 LIGAND

ESTEFANÍA ZACCA; MARÍA INÉS CRESPO; RACHEL ACLAND; EMILIANO ROSELLI; NICOLAS NUÑEZ; MARIANA MACCIONI; BELKYS A. MALETTO; MARÍA C. PISTORESI-PALENCIA; VICTOR GABRIEL MORON

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2015

1932-6203

The aging process is accompanied by altered immune system functioning and anincreased risk of infection. Dendritic cells (DCs) are antigen-presenting cells that play akey role in both adaptive and innate immunity, but how aging affects DCs and theirinfluence on immunity has not been thoroughly established. Here we examined thefunction of conventional DCs (cDCs) in old mice after TLR7 stimulation, focusing ontheir ability to cross-prime CD8+ T cells. Using polyU, a synthetic ssRNA analog, asTLR7 ligand and OVA as an antigen (Ag) model, we found that cDCs from old micehave a poor ability to stimulate a CD8+ T cell-mediated cytotoxic response. cDCs fromold mice exhibit alterations in Ag-processing machinery and TLR7 activation.Remarkably, CD8α+ cDCs from old mice have an impaired ability to activate naïveCD8+ T cells and, moreover, a lower capacity to mature and to process exogenous Ag.Taken together, our results suggest that immunosenescence impacts cDC function,affecting the activation of naïve CD8+ T cells and the generation of effector cytotoxic Tcells.