Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes
J. Clin. Invest. N. Manjunath, et al. 108:871 doi:10.1172/JCI13296 [
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Figure 1Effect of IL-2 and IL-15 on activated CD8 T cell proliferation and function. (
a and
b) All tested concentrations of IL-2 and IL-15 at 5 ng/ml or greater support cell proliferation. Cell proliferation was measured by viable cell counts (
a) or BrdUincorporation (
b) as described in Methods. In
b, histograms of BrdU incorporation by CD8
+ gated cells on day 3 of cytokine treatment are shown. Background staining obtained with isotype control is also shown for comparison. Similar results were seen for all treatment groups on each day for all 5 days tested (not shown). (
c) IL-2 induces increased cell death compared with IL-15. Cell death was measured by flow cytometric analysis of non-gated cells after staining with propidium iodide (PI). Shown are dot plots after 3 days of cytokine treatment. (
d) Both IL-2– and IL-15–treated cells acquire the ability for IFN-γ production. On day 7 following peptide stimulation and cytokine treatment, the cultures were restimulated with αCD3 for 6 hours, stained externally with αCD8 Cy 5, intracellularly with αIFN-γ Ab, and examined by flow cytometry. Less than 2% of unstimulated cells produced IFN-γ (not shown). (
e) Peptide primed cells cultured with IL-2 at concentrations of 10 ng/ml or greater exhibit high levels of cytotoxicity, whereas cells cultured with IL-2 at or below 5 ng/ml and all tested concentrations of IL-15 exhibit greatly diminished levels of cytotoxicity. On day 7 after stimulation, cultures were tested for specific killing of gp33 peptide-pulsed EL-4 target cells by chromium-release assay.