A single naive CD8+ T cell precursor can develop into diverse effector and memory subsets

Upon first antigen encounter, naive CD8(+) T cells get activated, clonally expand, and can develop into very distinct subsets, such as short-living effector cells or different memory subpopulations. The origin of subset diversification is currently unknown, but qualitative and quantitative differences in early signals received by individual precursor cells have been suggested as a major determinant. We show that transfer of a single antigen-specific naive T cell into a normal recipient mouse allowed recovery of clonally expanded daughter cells upon immunization. With this experimental approach, we conclusively demonstrated that a wide range of diversity could develop out of a single precursor cell, including different types of effector and memory T cells. Interestingly, single-cell-derived subset diversification resembled that of polyclonal T cell responses in the same individual mouse, although differentiation patterns differed between immunization strategies. These data implicate that subset diversification is both shaped and synchronized during the expansion phase.