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Understanding the lineage differentiation of memory T cells is a central question in immunology. We investigated this issue by analysing the expression of the chemokine receptor CCR7, which defines distinct subsets of naive and memory T lymphocytes with different homing and effector capacities^,, and antiviral immune responses to HIV and cytomegalovirus. Ex vivo analysis of the expression of CD45RA and CCR7 antigens, together with in vitro analysis of the cell-division capacity of different memory CD8⁺ T-cell populations, identified four subsets of HIV- and CMV-specific CD8⁺ T lymphocytes, and indicated the following lineage differentiation pattern: CD45RA⁺CCR7⁺ → CD45RA^-CCR7⁺ → CD45RA^CD45RA-CCR7^- → CD45RA⁺CCR7^-. Here we demonstrate through analysis of cell division (predominantly restricted to the CCR7⁺CD8⁺ T-cell subsets) that the differentiation of antigen-specific CD8⁺ T cells is a …