Figure 3.

Anti–CSF-1R (αCSF-1R) mAb treatment exacerbates GVHD without impairing donor hematopoietic cell engraftment. (A and B) C57BL/6 mice (n = 5–6/group) were injected i.p. with αCSF-1R (solid lines, diamond) or control rat IgG (dashed lines, triangle) on days −5 to −3, lethally irradiated (13 Gy), and injected i.v. on day 0 with 2.5 (open symbols) or 10 (closed symbols) × 10⁶ splenocytes plus 5 × 10⁶ BM cells isolated from BALB/c mice. As controls, syngeneic C57BL/6 CD45.2⁺ mice (open circle, n = 3/group) were treated with anti–CSF-1R (solid lines) or rat IgG (dashed lines) on days −5 to −3, lethally irradiated (13 Gy), and i.v. injected on day 0 with 2.5 × 10⁶ splenocytes plus 5 × 10⁶ BM cells isolated from C57BL/6 CD45.1⁺ congenic mice. Graphs show survival curves after transplant (A) and clinical GVHD scores reported as mean ± SEM (B). *, P < 0.005; **, P < 0.05 versus allogeneic rat IgG-treated groups. (C) H&E staining of liver (i, ii, and iii) and colon (iv, v, and vi) sections harvested 20 d after transplant from mice treated with αCSF-1R before syngeneic HCT (i and iv) or mice treated with rat IgG (ii and v) or αCSF-1R (iii and vi) before allo-HCT. Arrowheads show inflammatory infiltrates accumulating in liver tissue sections. Bars, 100 µm. (D) Pathological GVHD scores from syngeneic recipients (white bar, n = 6), allogeneic recipients treated with rat IgG (gray bar, n = 6), and allogeneic recipients treated with αCSF-1R (black bar, n = 6) are shown as mean ± SEM. Scores were analyzed on day 20 after transplant and calculated as the sum of the scores of liver, small intestine, and colon. *, P < 0.005. (E–G) White blood cells in peripheral blood were counted and analyzed by flow cytometry 11 d after allo-HCT. Percent donor chimerism among myeloid and lymphoid subsets (E), absolute numbers of total blood leukocytes (F), and circulating CD11b⁺ myeloid cells (G) are shown. Horizontal bars indicate mean. Data from one of two similar experiments were shown.