Effect of daily subcutaneous IL-15 in 2 immunocompetent macaques. (A) Schedule of IL-15 administration (15 μg/kg per day). Each represents a single daily dose of IL-15 (15 μg/kg), and the indicates a single daily dose of IL-15 (5 μg/kg). (B-C) Absolute numbers of WBCs, lymphocytes, and neutrophils (ANCs) in the peripheral blood before, during, and after IL-15 therapy. Absolute cell numbers of (B) WBCs (▵) and lymphocytes (●) per microliter of peripheral blood or (C) ANCs (◇) per microliter of peripheral blood and level of hemoglobin (■ Hb; gd/L) were determined on the indicated days. The arrows indicate the duration of the IL-15 administration. (D) Photomicrographs of hematoxylin and eosin–stained BM biopsy sections obtained after 7 days of treatment display hypoplasia and moderate focal hemorrhage (top, 5× objective). At higher magnification (middle, 40× objective), there is also fat necrosis and stromal edema. The scattered cells are erythroid precursors, lymphocytes, and macrophages. Normal clusters of maturing myeloid cells are absent (bottom, 100× objective). Photomicrographs were obtained with a Leica DFC320 camera on a Leica DM3000 microscope and processed with the Leica Application Suite version 3.1.0 (Leica Microsystems GmbH). Images were processed using Photoshop 7.0 software (Adobe Systems). Bars represent 100 micrometers. (E) Schedule of IL-15 administration for macaque 05078 (15 μg/kg per day). Each represents a single daily dose of IL-15. (F) Absolute cell numbers of WBCs (▵) and lymphocytes (●) per microliter of peripheral blood before, during, and after IL-15 therapy. (G) ANCs (◇) per microliter of peripheral blood and level of hemoglobin (■ Hb; gd/L) before, during, and after IL-15 therapy. indicates the duration of the IL-15 administration. (H) Photomicrographs of hematoxylin and eosin–stained marrow biopsy sections obtained after the IL-15 treatment as described in panel D. Bars represent 100 micrometers.