Pathways for memory T cell generation. (a) According to the most conventional model, memory T cells are derived from effector cells that revert to a quiescent state. (b) According to the new model of progressive T cell differentiation, the duration of antigenic stimulation and the type and amount of cytokines present during priming lead either to fully differentiated effector cells that home to peripheral tissues (blue) or to intermediate cells that are devoid of effector function and home to lymph nodes (green). In the system used by Manjunath et al. (7), these two cell types can be identified according to the differential expression of the T-GFP marker transgene and the lymph node–homing receptor CCR7. Both cell types are maintained in the memory pool (dotted arrows) and, upon secondary challenge, mediate immediate protection in nonlymphoid tissues or secondary responses in lymph nodes.