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H. El Hajj et al.
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Figure 3. A critical role for the loss of interleukin-10 production in arsenic/interferon-mediated eradication of adult T-cell leukemic-initiating cell activity. (A) Enzyme-linked immunosorbent assay (ELISA) on supernatant of homogenized CD25+ or CD25– sorted cells derived from the spleen of untreated (control) or arsenic trioxide (AS)/interferon alpha (IFNα)-treated primary mice. (B) ELISA on plasma of normal SCID mice (n=3; gray histogram) or SCID mice with adult T-cell leukemia/lymphoma (ATL) injected with 106 spleen cells derived from tax transgenic mice, and left untreated (n=5; black histogram) or treated with AS and IFNα from day 18 until day 21 (n=5; red histogram). (C) Survival of untreated secondary SCID mice injected with 106 or ten unsorted spleen cells from untreated (control) primary ATL mice (n=3 and n=4, respectively; black), 106 cells from primary mice treated with AS/IFNα for 3 days (n=8; red), or ten cells from untreated primary mice together with 106 cells from primary mice treated with AS/IFNα for 3 days (n=8; red-black dashed). (D) Survival and spleen weight of secondary recipient SCID mice injected with 106 unsorted spleen cells derived from primary mice treated with AS/IFNα. These secondary recipients were left untreated (control; black histograms) or treated with recombinant murine (Rec-m) interleukin 10 (IL-10) (red; n=7/condition). (E) Spleen weight and survival of primary ATL SCID mice (n=7/condition) treat- ed with anti-IL-10 antibodies (green histogram) or control isotype (black histogram). (F) Quantitative reverse transcriptase polymerase chain reaction analysis of homogenized CD25+ or CD25- sorted cells derived from the spleens of untreated primary mice or primary mice treated with anti-IL-10 antibodies. The t-test was per- formed to validate significance. *P≤0.05, **P≤0.01, and ***P≤0.001. P-values ≤0.05 were considered statistically significant.
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haematologica | 2021; 106(5)