Figure 2.
Figure 2. NKTL is driven by chronic TCR activation. (A) Borrelia induces chronic infection in p53−/− mice. Kinetics of anti-Borrelia IgG titer in p53−/− mice sera by enzyme-linked immunosorbent assay. Mice (n = 8-10 per group) were injected intradermally with control medium, heat-killed (HK) Borrelia, or live Borrelia, treated (blue line) or not (red line) with ceftriaxone (antibiotics; ATB) at 25 mg/kg, twice a day for 5 days, starting 10 days postinfection, to eradicate the bacteria after short-term infection. Data are mean ± SEM. P = .031 for kinetics between live Borrelia and live Borrelia + ATB, Kruskal-Wallis test. (B) Chronic infection is required to increase NKTL frequency. Lymphoma spectrum developed in p53−/− mice injected with control medium, live Borrelia, HK Borrelia, or live Borrelia + ATB. Only live Borrelia injection induced significantly more NKTL compared with control mice (P = .023, χ2 test). Of note, the number of tumors exceeded the total number of mice because some animals had several tumors (ie, a solid tumor and a lymphoma). Values in the center refer to the total numbers of lymphomas. (C) NKTL show features of chronically activated NKT cells. Flow cytometric analyses of NK1.1 and PD-1 expression on NKTL, showing a significant loss of NK1.1 (****P < .0001) and overexpression of PD-1 (**P = .002), Mann-Whitney U test. (D) NKT-activating glycolipids drive NKTL. Lymphoma spectra developed in PBS- and αGalCer-injected p53−/− mice. Mice were injected intraperitoneally every week with PBS or 4 µg of αGalCer. αGalCer injection induced significantly more NKTL compared with PBS. The P value was determined using the χ2 test. (E) NKTL depend on TCR-CD1d interaction for engraftment and survival in vivo. Survival curves of WT and CD1d−/− mice (n = 5) injected IV with 106 NKTL cells, showing the absence of lymphoma development in CD1d−/− recipient mice. All mice alive 100 days postinfection were euthanized. The P value was determined using the log-rank test. (F) Number of total liver NKT cells at sacrifice. ***P =.008, Mann-Whitney U test. TL, thymic lymphomas.

NKTL is driven by chronic TCR activation. (A) Borrelia induces chronic infection in p53−/− mice. Kinetics of anti-Borrelia IgG titer in p53−/− mice sera by enzyme-linked immunosorbent assay. Mice (n = 8-10 per group) were injected intradermally with control medium, heat-killed (HK) Borrelia, or live Borrelia, treated (blue line) or not (red line) with ceftriaxone (antibiotics; ATB) at 25 mg/kg, twice a day for 5 days, starting 10 days postinfection, to eradicate the bacteria after short-term infection. Data are mean ± SEM. P = .031 for kinetics between live Borrelia and live Borrelia + ATB, Kruskal-Wallis test. (B) Chronic infection is required to increase NKTL frequency. Lymphoma spectrum developed in p53−/− mice injected with control medium, live Borrelia, HK Borrelia, or live Borrelia + ATB. Only live Borrelia injection induced significantly more NKTL compared with control mice (P = .023, χ2 test). Of note, the number of tumors exceeded the total number of mice because some animals had several tumors (ie, a solid tumor and a lymphoma). Values in the center refer to the total numbers of lymphomas. (C) NKTL show features of chronically activated NKT cells. Flow cytometric analyses of NK1.1 and PD-1 expression on NKTL, showing a significant loss of NK1.1 (****P < .0001) and overexpression of PD-1 (**P = .002), Mann-Whitney U test. (D) NKT-activating glycolipids drive NKTL. Lymphoma spectra developed in PBS- and αGalCer-injected p53−/− mice. Mice were injected intraperitoneally every week with PBS or 4 µg of αGalCer. αGalCer injection induced significantly more NKTL compared with PBS. The P value was determined using the χ2 test. (E) NKTL depend on TCR-CD1d interaction for engraftment and survival in vivo. Survival curves of WT and CD1d−/− mice (n = 5) injected IV with 106 NKTL cells, showing the absence of lymphoma development in CD1d−/− recipient mice. All mice alive 100 days postinfection were euthanized. The P value was determined using the log-rank test. (F) Number of total liver NKT cells at sacrifice. ***P =.008, Mann-Whitney U test. TL, thymic lymphomas.

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