We demonstrated in previous studies that interleukin (IL) -2 supports in vitro cell proliferation of donor-derived cytotoxic T lymphocyte (CTL) lines directed against different types of leukemia blasts. The aim of this study was to compare the capacity of IL-15 with that of IL-2 in supporting the proliferation and cytotoxic activity of antileukemia CTL cultures, and their influence on T-cell memory compartment differentiation. Antileukemia CTL lines were generated using donor-derived dendritic cells pulsed with apoptotic leukemia blasts, in the presence of IL-12 and IL-7, during the primary culture, and expanded through 2 rounds of leukemia-specific stimulation and I round of antigen-independent expansion, each supplemented with either IL-2 or IL-15. Both IL-2-supplemented (IL-2-CTLs) and IL-15-supplemented (IL-15-CTLs) lines contained predominant numbers of CD45RA(-)/CCR7(-) effector memory (T-EM) and CD45RA(+)/CCR7(-) (TEMRA+) T cells. Significantly higher numbers (P < 0.05) of CD8-positive central memory T cells (T-CM), and higher expansion rate, together with comparable cytotoxic activity, were observed in IL-15-CTLS compared with IL-2-CTLs. Altogether, these results demonstrate that IL-15 enhances recovery of CTL activity, without loss of leukemia-directed specificity, and favors expansion of T-CM CDS-positive cells, expected to exhibit long-term survival and differentiation capacity in vivo in the presence of a limited amount of antigen.

Daudt, L., Maccario, R., Locatelli, F., Turin, I., Silla, L., Montini, E., Percivalle, E., Giugliani, R., Avanzini, M. A., Moretta, A., Montagna, D., Interleukin-15 favors the expansion of central memory CD8+ T cells in ex vivo generated, antileukemia human cytotoxic T lymphocyte lines, <<JOURNAL OF IMMUNOTHERAPY>>, 2008; 31 (4): 3-7. [doi:10.1097/CJI.0b013e31816b1092] [https://hdl.handle.net/10807/258441]

Interleukin-15 favors the expansion of central memory CD8+ T cells in ex vivo generated, antileukemia human cytotoxic T lymphocyte lines

Locatelli, Franco;
2008

Abstract

We demonstrated in previous studies that interleukin (IL) -2 supports in vitro cell proliferation of donor-derived cytotoxic T lymphocyte (CTL) lines directed against different types of leukemia blasts. The aim of this study was to compare the capacity of IL-15 with that of IL-2 in supporting the proliferation and cytotoxic activity of antileukemia CTL cultures, and their influence on T-cell memory compartment differentiation. Antileukemia CTL lines were generated using donor-derived dendritic cells pulsed with apoptotic leukemia blasts, in the presence of IL-12 and IL-7, during the primary culture, and expanded through 2 rounds of leukemia-specific stimulation and I round of antigen-independent expansion, each supplemented with either IL-2 or IL-15. Both IL-2-supplemented (IL-2-CTLs) and IL-15-supplemented (IL-15-CTLs) lines contained predominant numbers of CD45RA(-)/CCR7(-) effector memory (T-EM) and CD45RA(+)/CCR7(-) (TEMRA+) T cells. Significantly higher numbers (P < 0.05) of CD8-positive central memory T cells (T-CM), and higher expansion rate, together with comparable cytotoxic activity, were observed in IL-15-CTLS compared with IL-2-CTLs. Altogether, these results demonstrate that IL-15 enhances recovery of CTL activity, without loss of leukemia-directed specificity, and favors expansion of T-CM CDS-positive cells, expected to exhibit long-term survival and differentiation capacity in vivo in the presence of a limited amount of antigen.
2008
Inglese
Daudt, L., Maccario, R., Locatelli, F., Turin, I., Silla, L., Montini, E., Percivalle, E., Giugliani, R., Avanzini, M. A., Moretta, A., Montagna, D., Interleukin-15 favors the expansion of central memory CD8+ T cells in ex vivo generated, antileukemia human cytotoxic T lymphocyte lines, <<JOURNAL OF IMMUNOTHERAPY>>, 2008; 31 (4): 3-7. [doi:10.1097/CJI.0b013e31816b1092] [https://hdl.handle.net/10807/258441]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/258441
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