Checkpoints in thymocytopoiesis in aging: expression of the recombination activating genes RAG-1 and RAG-2

The study was designed to establish whether the ability to rearrange the T cell receptor (TCR) Vbeta genes is altered with age. We examined the expression of recombinase activating genes, RAG-1 and RAG-2, in the thymus of mice at different ages (2-24 months). A significant age-related decrease in RAG-1 and RAG-2 expression was observed in the thymocytes from the age of 12 months and over. To find out if this decrease is determined in the thymocyte progenitors or induced by the thymic microenvironment, we co-cultured lymphoid depleted fetal thymus (FT) explants with bone marrow cells, or immature thymocytes, from young and old mice. The developing thymocytes were examined at different time intervals during the first week of culture. Whereas cells derived from the immature thymocytes of the old donors failed to express RAG-1 and RAG-2, compared to the young, the bone marrow derived cells of both age groups did show this expression, and there was no difference in Vbeta rearrangement of the TCR. Our study indicates that T cell progenitors in the aging bone marrow retain the potential to give rise to T cells with TCR rearrangements, and the expression is determined by the thymic stroma.