AGING OF THE RECIPIENTS BUT NOT OF THE BONE-MARROW DONORS ENHANCES AUTOIMMUNITY IN SYNGENEIC RADIATION CHIMERAS

Young and old mice have been lethally irradiated and injected with syn geneic bone marrow cells from young or old donors to investigate wheth er self reactivity in old mice results from age-related damage of the radioresistant stromal cells and/or of the bone marrow hematopoietic c ells. Thymus and spleen cell repopulations and mitotic responses at 3 months after irradiation are lower in old than in young recipients, su ggesting age-related accumulation of stromal cell damage in the thymus as well as in other central and peripheral lymphoid tissues. The same efficiency of bone marrow cells from young and old donors to repopula te the thymus and spleen in recipients of equal age rules out the detr imental effects of aging on stem cells as well as T and B cell precurs ors. The serum concentration of auto-antibody and glomerular lesions a t 3 and 9 months after irradiation were more pronounced in old than in young recipients and displayed no difference in recipients of equal a ge, regardless of the age of the bone marrow cell donors. These findin gs support the possibility that age-related damage of stromal cells in duces disregulation of the immune system leading to autoimmune phenome na. (C) 1997 Elsevier Science Ireland Ltd.