Figure 6
Figure 6. Ibrutinib functionally restores immunity in a leukemia/listeriosis mouse model. (A) Schematic representation of the leukemia/listeriosis mouse experiment time course. Mice were engrafted via intravenous injection with leukemic cells purified from the spleen of a EµTCL1 transgenic animal. Engrafted mice were randomly divided between vehicle and ibrutinib (25 mg/kg/day) groups on day 7. IV L monocytogenes-OVA inoculation (5000 CFU) was conducted 14 days after engraftment. Rechallenge began 14 days after initial inoculation and consisted of a single 5000 CFU L monocytogenes OVA intravenous injection. Mice were sacrificed at day 32 and tissues were collected for memory cell analysis. (B) Time course analysis of OVA major histocompatibility complex I tetramer-positive peripheral CD8 T cells from leukemia/listeriosis mouse study. A total of 5000 CFU of OVA-expressing L monocytogenes was injected at day 0. Statistical analysis for day 8 mean is presented (**P = .0052; *′P = .0438 for repeat experiment). Error bars represent SEM. (C) Analysis of OVA-tetramer+ CD8+ T cells within the spleen of animals killed on day 32 of the leukemia/listeria infection experiment. Data are displayed as percentage of CD8+ T cells. Error bars represent SEM. (D) Analysis of CD8+CD62L+ central memory cells within the spleen of mice killed at day 32 of the leukemia/listeria infection experiment. Data are presented as the average of the total CD8+ population. Error bars represent SEM. (E) Analysis of CD4+CD62L+ central memory cells within the spleen of mice killed at day 32 of the leukemia/listeria infection experiment. Data are presented as the average of the total CD4+ population. Error bars represent SEM.

Ibrutinib functionally restores immunity in a leukemia/listeriosis mouse model. (A) Schematic representation of the leukemia/listeriosis mouse experiment time course. Mice were engrafted via intravenous injection with leukemic cells purified from the spleen of a EµTCL1 transgenic animal. Engrafted mice were randomly divided between vehicle and ibrutinib (25 mg/kg/day) groups on day 7. IV L monocytogenes-OVA inoculation (5000 CFU) was conducted 14 days after engraftment. Rechallenge began 14 days after initial inoculation and consisted of a single 5000 CFU L monocytogenes OVA intravenous injection. Mice were sacrificed at day 32 and tissues were collected for memory cell analysis. (B) Time course analysis of OVA major histocompatibility complex I tetramer-positive peripheral CD8 T cells from leukemia/listeriosis mouse study. A total of 5000 CFU of OVA-expressing L monocytogenes was injected at day 0. Statistical analysis for day 8 mean is presented (**P = .0052; *′P = .0438 for repeat experiment). Error bars represent SEM. (C) Analysis of OVA-tetramer+ CD8+ T cells within the spleen of animals killed on day 32 of the leukemia/listeria infection experiment. Data are displayed as percentage of CD8+ T cells. Error bars represent SEM. (D) Analysis of CD8+CD62L+ central memory cells within the spleen of mice killed at day 32 of the leukemia/listeria infection experiment. Data are presented as the average of the total CD8+ population. Error bars represent SEM. (E) Analysis of CD4+CD62L+ central memory cells within the spleen of mice killed at day 32 of the leukemia/listeria infection experiment. Data are presented as the average of the total CD4+ population. Error bars represent SEM.

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