The hallmark of the adaptive immune system is the development of an immunological memory that is capable of responding faster and to a greater magnitude upon reactivation with the same pathogen compared to the first encounter. This enhanced response is generally attributed to a larger number of precursor cells as well as a faster expansion of memory T cells. Here we assessed the in vitro proliferation and survival dynamics of memory OT-I cells in response to antigenic and co-stimulation to test the hypothesis that memory T cells follow different proliferation kinetics compared to their naive counterparts.
Unexpectedly we found that memory and naive T cells expand at identical rates after in vitro stimulation with αCD3. However, differences to external stimuli could be observed. IL-2 and αCD28 had the biggest impact on naive cells and to a lesser degree on memory cells. In contrast IL-7 promoted the division progression of memory cells but not of naive cells. IL-15 did not affect the division progression of either cell type.
In summary, here we show that memory and naive CD8 T cells have the identical intrinsic proliferation rates, but respond differentially and discretely to external factors such as αCD28, IL-2 or IL-7. The differential response to external factors might help to explain differences in cell expansion after activation observed in vitro and in vivo experiments and can be used to target immune therapies.