Maintenance of CD8(+) memory T lymphocytes in the spleen but not in the bone marrow is dependent on proliferation

It is current belief that numbers of CD8(+) memory T lymphocytes in the memory phase of an immune response are maintained by homeostatic proliferation. Here, we compare the proliferation of CD8(+) memory T lymphocytes, generated by natural infections and by intentional immunization, in spleen and bone marrow (BM). Fifty percent of CD8(+) memory T lymphocytes in the spleen are eliminated by cyclophosphamide within 14 days, indicating that numbers of at least 50% of splenic CD8(+) memory T lymphocytes are maintained by proliferation. The numbers of CD8(+) memory T lymphocytes in the BM, however, were not affected by cyclophosphamide. This stability was independent of circulating CD8(+) memory T cells, blocked by FTY720, showing that BM is a privileged site for the maintenance of memory T lymphocytes, as resident cells, resting in terms of proliferation.