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Targeting IL-10 abrogates ATL LIC
A
in arsenic/interferon-mediated
C
AS/IFNα-treated (red tograms) primary SCID mice wth adult T-cell leukemia/lymphoma (ATL). The secondary mice were treated with clodronate or their corresponding empty liposomes, or anti-NK1.1 antibody or mouse IgG isotype control starting on day 3 after injection of cells (n=5/condition). (C) Enzyme- linked immunosorbent assay on supernatant of homogenized CD25+ or CD25– sorted cells derived from the spleen of untreated (control) or AS/IFNα-treated primary mice for pro-inflammatory cytokines (IL-12 and IFNγ), as well as the pro-inflammatory monocyte chemoattractant protein-1 (MCP- 1/CCL2) and the macrophage inflammatory protein 1-alpha (MIP-1α) chemokines. The t-test was performed to validate signif- icance. *P≤0.05, **P≤0.01, and ***P≤0.001. P-values ≤0.05 were considered statistically sig- nificant.
B
+
F4/80 cells (macrophages)
Figure 2. A critical role for natu-
ral killer cells and macro-phages
suppression of adult T-cell
leukemic-initiating cell activity.
(A) The same experimental
design as shown in Figure 1A
was followed. Histograms repre-
sent survival of untreated sec-
ondary SCID mice injected with
106 CD25+ cells from untreated
(control; n=5 black histograms)
or arsenic trioxide (AS)/interfer-
on alpha (IFNα)-treated primary
mice (n=5 red histograms); sur-
vival of untreated secondary
SCID mice injected with 106
CD25+ cells from untreated
primary mice and 25,000 CD25–
CD335+ NK cells from AS/IFNα-
treated primary mice (n=3 verti-
cally dashed red histogram with
black contour line); survival
of untreated secondary SCID
mice injected with 106 CD25+
cells from AS/IFNα-treated pri-
mary mice and 25,000 CD25–
CD335+ cells from AS/IFNα-
treated primary mice (n=3 verti-
cally dashed red histogram with
red contour line); survival of
untreated secondary SCID mice
injected with 106 CD25+ cells
from untreated primary mice
and 25,000 CD25–CD11b+
from AS/IFNα-treated primary mice (n=4 oblique dashed red histogram with black contour line); and survival of untreated secondary SCID mice injected with 106 CD25+ cells from AS/IFNα-treated primary mice and 25,000 CD25–CD11b+F4/ 80+ cells from AS/IFNα-treated primary mice (n=4 oblique dashed red histogram with red contour line). (B) Secondary SCID mice were injected with 106 unsorted spleen cells from untreated (black histograms) or
his-
haematologica | 2021; 106(5)
1447