UCSF

Following acute infection, rare naive T-cells expand in number, differentiate into effector cells, and acquire functions to combat the pathogen. Resolution of the response results in the death of a majority of the effector cells and survival of a small population of memory T-cells with properties that contribute to increased protection from reinfection. Many T-cell intrinsic and extrinsic signals have been found to enhance or detract from effector and memory cell differentiation. It has been postulated that strength of antigen-receptor signals influences subsequent fate of naive T-cells during the effector to memory transition, however, the nature of these signals and mechanisms of action are unclear.

An approach was taken to genetically mark populations of T-cells in mice that differed in the amount of antigen-receptor stimulation. By using this method with the well characterized acute lymphocytic choriomeningitis virus (LCMV) model of infection, the fate of antigen-specific CD4+ effector T-cells generated as a result of different amounts of TCR signal strength was determined in vivo. Our findings provide in vivo evidence in support of a deterministic model of CD4+ memory generation following acute viral infection where programming events driven in part by the strength of initial antigen-receptor stimulation influence the fate of responding CD4+ cells during the transition to memory.