Figure 3.
Donor T-cell–derived GM-CSF drives lethal GVHD. (A) Lethally irradiated Balb/c mice were transplanted with B6 BM alone (n = 9) or together with B6 spleen cells (adjusted to yield an αβ+ T-cell dose of 0.85 × 106). Animals receiving adjunctive splenocytes were treated intraperitoneally with 0.5 mg rat IgG (n = 15) or anti-GM-CSF antibody (M250; n = 15) weekly for 5 weeks. Results are from 3 experiments. (B-C) Irradiated Balb/c were transplanted with BM alone from B6 (n = 6) or GM-CSF−/− (n = 6) donors or BM and spleen cells from B6 (n = 10) or GM-CSF−/− animals (n = 10). Overall survival is depicted in panel B, and serial weight curves expressed as a percentage of pretransplant weight in panel C. Results are from 2 experiments. (D) Balb/c mice were transplanted with B6 BM cells (n = 15), B6 BM plus B6 spleen cells (adjusted to yield an αβ+ T cell dose of 0.85 × 106; n = 20), B6 BM plus an equivalent number of GM-CSF−/− spleen cells (n = 25), or GM-CSF−/− BM and B6 spleen cells (n = 25). Overall survival is shown. Results are cumulative results from 5 experiments. (E-H) Balb/c mice were transplanted with BM and spleen cells (adjusted to yield an αβ+ T cell dose of 0.8 × 106) from B6 or GM-CSF−/− mice. Balb/c mice transplanted with B6 BM only served as controls. (E) Representative hematoxylin and eosin-stained sections of the liver, lung, and colon of transplant recipients from each cohort. Original magnification is 100× for photomicrographs. (F) Pathological scores of liver, lung, and colon tissue harvested from animals 21 days posttransplantation using a semiquantitative scoring system are depicted. Data are from 3 experiments with 9 to 15 mice/group. (G) The total number of donor-derived CD4+ or CD8+ T cells isolated from the liver, lung, and colon is shown on day 21 posttransplantation. Data are from 3 independent experiments (n = 13-15/group). (H) The total number of donor-derived CD4+ IFN-γ+ or CD8+ IFN-γ+ T cells in the colon 21 days posttransplantation. Results are from 2 experiments (n = 8 mice/group). *P < .05; **P < .01; ***P < .001; ****P < .0001.

Donor T-cell–derived GM-CSF drives lethal GVHD. (A) Lethally irradiated Balb/c mice were transplanted with B6 BM alone (n = 9) or together with B6 spleen cells (adjusted to yield an αβ+ T-cell dose of 0.85 × 106). Animals receiving adjunctive splenocytes were treated intraperitoneally with 0.5 mg rat IgG (n = 15) or anti-GM-CSF antibody (M250; n = 15) weekly for 5 weeks. Results are from 3 experiments. (B-C) Irradiated Balb/c were transplanted with BM alone from B6 (n = 6) or GM-CSF−/− (n = 6) donors or BM and spleen cells from B6 (n = 10) or GM-CSF−/− animals (n = 10). Overall survival is depicted in panel B, and serial weight curves expressed as a percentage of pretransplant weight in panel C. Results are from 2 experiments. (D) Balb/c mice were transplanted with B6 BM cells (n = 15), B6 BM plus B6 spleen cells (adjusted to yield an αβ+ T cell dose of 0.85 × 106; n = 20), B6 BM plus an equivalent number of GM-CSF−/− spleen cells (n = 25), or GM-CSF−/− BM and B6 spleen cells (n = 25). Overall survival is shown. Results are cumulative results from 5 experiments. (E-H) Balb/c mice were transplanted with BM and spleen cells (adjusted to yield an αβ+ T cell dose of 0.8 × 106) from B6 or GM-CSF−/− mice. Balb/c mice transplanted with B6 BM only served as controls. (E) Representative hematoxylin and eosin-stained sections of the liver, lung, and colon of transplant recipients from each cohort. Original magnification is 100× for photomicrographs. (F) Pathological scores of liver, lung, and colon tissue harvested from animals 21 days posttransplantation using a semiquantitative scoring system are depicted. Data are from 3 experiments with 9 to 15 mice/group. (G) The total number of donor-derived CD4+ or CD8+ T cells isolated from the liver, lung, and colon is shown on day 21 posttransplantation. Data are from 3 independent experiments (n = 13-15/group). (H) The total number of donor-derived CD4+ IFN-γ+ or CD8+ IFN-γ+ T cells in the colon 21 days posttransplantation. Results are from 2 experiments (n = 8 mice/group). *P < .05; **P < .01; ***P < .001; ****P < .0001.

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