EFFECT OF AGING ON HOST DENDRITIC CELL (DC) NUMBERS AND FUNCTION FOLLOWING HEMATOPOIETIC STEM CELL CONDITIONING REGIMEN (102.8)

Abstract

Abstract Graft versus host disease (GVH) incidence and severity increases with older patient age. Host DC are responsible for initiating GVH, likely from activation during transplant conditioning. In this study, young (8–14 wk) and older (12–16 mo) mice were treated with conditioning of lethal irradiation (950–1100 cGy) and assessed 6 h and 18 h later for changes in DC costimulatory molecule expression and cytokine secretion. Older mice had slightly higher numbers of splenic classical DC (cDC; CD11chi Cl II+ B220-) and plasmacytoid DC (pDC; CD11clo Cl IIlo B220+) both before and after irradiation. No differences were observed in CD40, CD80, or CD86 expression between young and older mice, either before or 6 h after irradiation. IL-12, IFN?, and TNF? producing cDC were more numerous in young than in older untreated mice. These cells decreased in young mice and increased in older mice at 6 and 18 h after irradiation. IL-12, IFN?, and TNF? producing pDC were more frequent in older than in young mice prior to irradiation, and both older and young mice had increased frequency of cells producing these cytokines after irradiation. Older mice had a higher frequency of IL-10+ cDC and pDC prior to irradiation. After irradiation, young mice had a higher frequency of IL-10+ cells. These findings indicate the balance of cytokine production in older mice after conditioning with irradiation is shifted to stimulatory rather than suppressive cytokines