The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses

Memory cd8 t cells provide protection to immune hosts by eliminating pathogen-infected cells during re-infection. while parameters influencing the generation of primary (1°) cd8 t cells are well established,the factors controlling the development of secondary (2°) cd8 t cell responses remain largely unknown. here,we address the mechanisms involved in the generation and development of 2° memory (m) cd8 t cells. we observed that the time at which 1° m cd8 t cells enter into immune response impacts their fate and differentiation into 2° m cd8 t cells. late-entry of 1° m cd8 t cells into an immune response (relative to the onset of infection) not only facilitated the expression of transcription factors associated with memory formation in 2° effector cd8 t cells,but also influenced the ability of 2° m cd8 t cells to localize within the lymph nodes,produce il-2,and undergo ag-driven proliferation. the timing of stimulation of 1° m cd8 t cells also impacted the duration of expression of the high-affinity il-2 receptor (cd25) on 2° effector cd8 t cells and their sensitivity to il-2 signaling. importantly,by blocking or enhancing il-2 signaling in developing 2° cd8 t cells,we provide direct evidence for the role of il-2 in controlling the differentiation of ag-driven 2° cd8 t cell responses. thus,our data suggest that the process of 1° m to 2° m cd8 t cell differentiation is not fixed and can be manipulated,a notion with relevance for the design of future prime-boost vaccination approaches. © 2015 khan et al.