AGE-RELATED CHANGES IN PRIMATE DENDRITIC CELL FUNCTION

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Healthy elderly individuals demonstrate vulnerability to infectious diseases compared with young adults, which reflects senescence of the immune system. Dendritic cells (DC) are critical elements of both the innate and adaptive immune system. We hypothesize that DC function may be altered in the old so as to contribute to the relatively immunocompromised state observed in this population. The Rhesus macaque (Macaca mulatta) provides a valuable model for addressing this hypothesis because reagents exist for performing detailed immunological analysis and the Rhesus monkey provides a reproducible and closely parallel model of the aging immune system. We propose to assess age-related changes in DC by cross-sectional, as well as longitudinal, comparison between different age groups of macaques. The specific aims are: 1) To evaluate the effect of aging on DC function by measuring: (i) numbers and function of precursor DC (pDC1 and IPC/pDC2) in the peripheral blood; (ii) cell surface molecule and cytokine expression of monocyte-derived immature DC (iDC) and mature DC (mDC) isolated from the peripheral blood; and (iii) gene expression pattern of precursor DC and monocyte-derived iDC and mDC using cDNA microarray analysis, and analyzed using bioinformatics. 2) To evaluate the effect of aging on DC antigen uptake and migration, in vitro and in vivo. 3) To evaluate the effect of aging on DC antigen processing and presentation function in vitro (antigen presentation assays of monocyte-derived DC); and following antigen priming in vivo (evaluation of draining lymph node DC for ex vivo APC function). These studies will provide insight into the role of DC in immune senescence that in turn may be used to improve vaccination outcomes and the health of the elderly.