Interleukin-15 favors the expansion of central memory CD8+ T cells in ex vivo generated, antileukemia human cytotoxic T lymphocyte lines.
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 1 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 (TEM) and CD45RA/CCR7 (TEMRA+) T cells. Significantly higher numbers (P<0.05) of CD8-positive central memory T cells (TCM), 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 TCM CD8-positive cells, expected to exhibit long-term survival and differentiation capacity in vivo in the presence of a limited amount of antigen.
Daudt
Liane
L
Laboratorio d'Immunologia dei Trapianti e Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Brazil.
Maccario
Rita
R
Locatelli
Franco
F
Turin
Ilaria
I
Silla
Lucia
L
Montini
Enrica
E
Percivalle
Elena
E
Giugliani
Roberto
R
Avanzini
Maria Antonietta
MA
Moretta
Antonia
A
Montagna
Daniela
D
D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy
D019409:Interleukin-15; D007371:Interferon-gamma