C57BL/6 mice were infected i.v. with either 10³ colony-forming unit Lm-ova or 10⁵ PFU vesicular stomatitis virus-ova. Five days later, Ova/K^b-specific CD8⁺ T cells in the spleen were phenotyped using the cell surface molecules KLRG1 and CD127 to identify the early effector cells (EECs), short-lived effector cells (SLECs), and memory precursor effector cells (MPEC) populations. Intracellular granzyme B levels were then examined within each population and compared with naive CD8⁺ T cells (CD11a^low CD44^low). Granzyme B levels for naive CD8⁺ T cells are displayed in the filled gray histogram, while the granzyme B levels in the Ova/K^b-specific effector CD8⁺ T-cell populations are in the open histograms: EECs (red line), SLECs (black line), and MPECs (blue line).

Early activation of the naive CD8⁺ T-cell population results in the generation of the early effector cell (EEC) population, which begins differentiation into short-lived effector cells (SLEC) and memory precursor effector cells (MPECs). These early differentiation events (i.e., the first 3–4 days) correspond to times when high levels of interleukin (IL)-12, IL-15, and interferon-α/-β are found. The next cytokine that appears to work on the responding CD8⁺ T-cell population is IL-2, as the high-affinity IL-2 receptor is only expressed transiently during this time period (i.e., days 3–5). IL-2 not only works to amplify the whole CD8⁺ T-cell population but also enhances the differentiation of the EEC population to SLECs. Around the peak of the CD8⁺ T-cell response, high levels of transforming growth factor (TGF)-β can be found. TGFβ will oppose the actions of homeostatic levels of IL-15 and promote the preferential apoptosis of the EEC and SLEC populations leaving only the MPEC population. The levels of IL-15 in the tissues will also regulate this process as SLECs are exquisitely dependent on IL-15 for their survival, whereas the MPEC population is more dependent on IL-15 for long-term homeostatic proliferation and is dependent on IL-7 for survival.

Activation of both CD4⁺ and CD8⁺ T cells by dendritic cells will occur simultaneously in lymphoid organs. For both CD4⁺ and CD8⁺ T cells, activation and subsequent proliferation is mediated by T-cell receptor:pMHC (peptide: major histocompatibility complex) interactions and costimulatory molecules, such as CD28:CD80/86. When the ‘helper’ CD4⁺ T-cell population reaches a critical mass enough paracrine IL-2 will be produced to ‘help’ maintain the expansion and differentiation of CD8⁺ T-cell responders. IL-2 will act on the CD25⁺ early effector cells (EECs) population and further upregulate the expression of CD25, at which time it will help direct the differentiation of the EEC. IL-2 will promote the preferential differentiation toward short-lived effector cells, but is likely important in the expansion of all effector cells.