期刊
CYTOKINE
卷 36, 期 3-4, 页码 148-159出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2006.11.008
关键词
T cells; cytotoxic; cytokines; cell activation; cell proliferation; cytotoxicity; granzyme B
资金
- NCI NIH HHS [T32 CA009563, T32 CA009563-17, R01 CA038942, R01 CA038942-18, T32 CA09563, T32 CA009563-18, R01 CA38942-19, R01 CA038942-19] Funding Source: Medline
- NCRR NIH HHS [P20 RR016464] Funding Source: Medline
The purpose of these studies was to determine the minimal requirements to induce granzyme B, cytotoxic granules and perforin-dependent lytic capacity. To our surprise, both IL-2 and IL-15 induced not only proliferation, but also profound granzyme B and lytic capacity from CD8+ T cells in the absence of antigen or TCR-stimulation. Mouse splenocytes were incubated with mouse r-IL-2 or r-IL-15 for three days, tested by anti-CD3 redirected lysis and examined for intracellular granzyme B and for T cell activation markers. With 10(-8) M IL-2 or IL-15, there was excellent lytic activity at 1:1 effector to target ratios mediated by T cells from wild-type but not from perforin-gene-ablated mice, consistent with multiclonal activation. Lower interleukin concentrations induced less lytic activity. Granzyme B was undetectable on day 0, and greatly elevated on day 3 in CD44(hi) CD8+ T cells as detected by flow cytometry. Cytokines alone elevated the granzyme B as much as concanavalin A combined with the cytokines. Some ex vivo CD8(+) T cells were CD122(+), as were the cultured granzyme B+ cells, thus both populations had low-affinity receptors for the interleukins. Only some of the activated cells were proliferating as detected by CFSE labeling. When the cytokines were withdrawn, the cells lost lytic activity within 24 h and then within the next 24 h, died. Our results suggest that high concentrations of either IL-2 or IL-15 will activate the lytic capacity and granzyme B expression of many T cells and that antigen recognition is not required. (c) 2006 Elsevier Ltd. All rights reserved.
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