Aging Effects on Dendritic Cells after Total Body Irradiation in Mice

ABSTRACT

BACKGROUND: It is still obscure how dendritic cells (DCs) can orchestrate whole immune reactions according to the host age. We studied changes of murine splenic DCs after total body irradiation (TBI), with regards to age. METHODS: Young (8~14 wk) and old (12~16 mo) C57Bl/6 mice were irradiated with a dose of 1,100 cGy and were assessed 6 h later for phenotypic and functional changes of the DCs. The mean fluorescence intensities and cytokine producing cell proportions were analyzed with the student's t-test. RESULTS: Interleukin-12 (IL-12), interferon (IFN gamma) and tumor necrosis factor (TNF alpha) producing classical DCs (cDCs) were more numerous in the young untreated mice than in the old mice. However, the number of these cells decreased in the young mice and increased in the old mice after TBI. IL-12, IFN gamma and TNF alpha producing plasmacytoid DCs (pDCs) were more frequent in the old mice than in the young mice before TBI both mice showed an increased frequency of cells producing these cytokines after TBI. Overall, the highest numbers of cDCs and pDCs producing IL-12, IFN gamma and TNF alpha were present in the old mice after TBI. In both the cDC and pDC populations, the old mice had a higher frequency of IL-10+ cells prior to TBI. After irradiation, the young mice had a higher frequency of IL-10+ cells. CONCLUSION: With TBI, the DCs showed dramatic differences between young and old mice. Young mice turned to an immuno-suppressive response whereas the old mice changed to an immuno-stimulation of DCs after TBI. From these dramatic aging effects, we hope to explain the different frequencies and severities of acute GvHD after allogeneic hematopoietic stem cell transplantation according to host age.