Figure 2.
Inhibition of BCL6 corepression activity can treat established BO cGVHD not sclerodermatous cGVHD. (A-E) BO cGVHD was established and assessed as described above. On days 28 to 56, mice were treated with vehicle or 50 mg/kg 79-6. (A) Pulmonary function test results demonstrate that 79-6 is able to improve pulmonary function compared with cGVHD control. (B-C) Frequency of GC B cells not TFH is decreased in mice treated with 79-6. (D) Immunoglobulin deposition in the lung had a trend toward being decreased (IgG in Fitc and Dapi; original magnification ×20). (E) Collagen deposition in the lung was reduced with 79-6 treatment (Masson's trichrome stain; original magnification ×20). (F) Histopathology scores of hemotoxylin and eosin–stained tissue sections demonstrated that 79-6 did not improve organ damage in liver and colon. (A-B) Data are pooled from 3 experiments, 4 to 7 mice per group per experiment. (C) Pooled from 2 experiments, 5 to 8 mice per group per experiment. (D-F) Representative from 1 experiment, 3 to 5 mice per group. (G-I) Sclerodermatous cGVHD was induced in Balb/c recipients treated on day 21 with irradiation (7 Gy by radiograph) and infusion of B10.D2 BM alone (BM only) or with B10.D2 purified T cells (scleroderma). With the appearance of significant difference in skin scores (∼day 21), mice began treatment with 50 mg/kg 79-6. (G) Analysis of frequency of GC B cells in spleens taken day 50 after transplant. Frequency of GC B cells in scleroderma mice demonstrates that the GC center is not a significant contributor to this disease. (H) Skin scores were determined twice weekly as described.18 Treatment with 79-6 was unable to improve skin manifestations of disease. (I) Cytokine analysis from pooled (2 mice per sample) lymph node harvested at day 50 after transplant. Cells were stimulated with phorbol myristate acetate (PMA)/ionomycin for 5 hours and then stained. 79-6 treatment did not change the frequencies of IL-17A+ or IFNg+ CD4+ cells from that of scleroderma controls. (G-I) Data are pooled from 2 experiments, 7 to 10 mice per group per experiment. The unpaired Student t test was used when comparing 2 groups. Error bars indicate SEM. Significance: *P < .05; **P < .01; ***P < .001.

Inhibition of BCL6 corepression activity can treat established BO cGVHD not sclerodermatous cGVHD. (A-E) BO cGVHD was established and assessed as described above. On days 28 to 56, mice were treated with vehicle or 50 mg/kg 79-6. (A) Pulmonary function test results demonstrate that 79-6 is able to improve pulmonary function compared with cGVHD control. (B-C) Frequency of GC B cells not TFH is decreased in mice treated with 79-6. (D) Immunoglobulin deposition in the lung had a trend toward being decreased (IgG in Fitc and Dapi; original magnification ×20). (E) Collagen deposition in the lung was reduced with 79-6 treatment (Masson's trichrome stain; original magnification ×20). (F) Histopathology scores of hemotoxylin and eosin–stained tissue sections demonstrated that 79-6 did not improve organ damage in liver and colon. (A-B) Data are pooled from 3 experiments, 4 to 7 mice per group per experiment. (C) Pooled from 2 experiments, 5 to 8 mice per group per experiment. (D-F) Representative from 1 experiment, 3 to 5 mice per group. (G-I) Sclerodermatous cGVHD was induced in Balb/c recipients treated on day 21 with irradiation (7 Gy by radiograph) and infusion of B10.D2 BM alone (BM only) or with B10.D2 purified T cells (scleroderma). With the appearance of significant difference in skin scores (∼day 21), mice began treatment with 50 mg/kg 79-6. (G) Analysis of frequency of GC B cells in spleens taken day 50 after transplant. Frequency of GC B cells in scleroderma mice demonstrates that the GC center is not a significant contributor to this disease. (H) Skin scores were determined twice weekly as described.18 Treatment with 79-6 was unable to improve skin manifestations of disease. (I) Cytokine analysis from pooled (2 mice per sample) lymph node harvested at day 50 after transplant. Cells were stimulated with phorbol myristate acetate (PMA)/ionomycin for 5 hours and then stained. 79-6 treatment did not change the frequencies of IL-17A+ or IFNg+ CD4+ cells from that of scleroderma controls. (G-I) Data are pooled from 2 experiments, 7 to 10 mice per group per experiment. The unpaired Student t test was used when comparing 2 groups. Error bars indicate SEM. Significance: *P < .05; **P < .01; ***P < .001.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal