After activation within a lymphoid tissue, T lymphocytes enter the blood, where they circulate and then re-enter many organs. However, they predominantly end up in the tissue of origin, a phenomenon so far thought to be caused by organ-specific homing. We analyzed the fate of T cells from different sources stimulated via the T cell receptor and CD28 and then injected intravenously into rats. Our results showed that preferential proliferation and reduced apoptosis, rather than preferential immigration, were responsible for the accumulation of activated T cells in the tissue of origin, explaining how immune responses can spread from site to site but still be restricted to certain regions. Manipulating the life span of such cells might be a promising approach to influencing immune responses.