Defects in stem/progenitor cells increase with age and have been linked to the development of autoimmune disease. The widely studied B/W mice develop renal disease at 5 months and die between 7 and 12 months. We studied IL-2 and IL-7 stimulated proliferation and differentiation of bone marrow lymphoid progenitor cells (BMMC) in young (3 months) and old (8 months) mice. BMMC isolated from the femur of young and old mice were treated with rIL-2 for proliferation and differentiation of T cell progenitors, and rIL-7 for pre-B cells. Using the methylcellulose colony forming unit (CFU) assay, the number of T and B progenitor cell CFU in young mice was similar (23±2.9 and 22±5.2 per = 5x10 BMMC). In old mice, there were 10±3.3 CFU for IL-2 (p<0.01) vs. 37±6.8 for IL-7 (p<0.05). These results indicate that IL-2-dependent preT-cells decrease with age while B cell progenitors increase with age. FACS analysis of differentiation of T and B cell lineage in 5-day cultures of BMMC with IL-2 and IL-7 revealed changes in low density cell surface molecules. The percentages from old and young T cells were as follows: CD3+: 79% vs 99%; CD4+: 8% vs 58%; CD8+: 3% vs 12%. For B cell lineage, the percentages were CD45/B220+: 86% vs 100%; slg+: 20% vs 79%; and IgA+: 17% vs 95%. Finally, IL-2 and GM-CSF gene expression in BMMC as measured by RT-PCR were both decreased in old mice. These results indicate that B cell progenitor proliferation increases with age, while T and B cell differentiation decreases. Thus, T cell proliferation and differentiation may be a key factor in the development of murine autoimmune disease.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology