Influence of huPBMC dose titration and macrophage depletion on engraftment of human CD45+ cells, CD4/CD8 ratios, and fractions of CD4+ CD8+ cells in peripheral blood
. | Day 7 . | . | . | Day 14 . | . | . | Day 21 . | . | . | Day 62 . | . | . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PBMCs, × 106 . | hCD45 . | CD4/CD8 . | CD4+CD8+ . | hCD45 . | CD4/CD8 . | CD4+CD8+ . | hCD45 . | CD4/CD8 . | CD4+CD8+ . | hCD45 . | CD4/CD8 . | CD4+CD8+ . | ||||||||
| A + lipo, % | ||||||||||||||||||||
| 5 | 3.5 | 4.1 | 0 | 42.0 | ND | 5.0 | 61.5 | 0.1 | 8.0 | 3.5 | 1.3 | 4.0 | ||||||||
| 5 | 0.3 | 2.4 | 0 | 24.0 | 0.4 | 20.0 | 19.0 | 0.1 | 13.0 | 0.8 | 0 | 25.0 | ||||||||
| 5 | 0.3 | 6.3 | 0 | 35.0 | 1.2 | 9.0 | 83.0 | 0.8 | 5.0 | — | — | — | ||||||||
| 10 | 5.0 | 1.9 | 1.0 | 70.5 | 2.7 | 5.0 | — | — | — | — | — | — | ||||||||
| 10 | 6.0 | 2.2 | 0.3 | 77.5 | 1.5 | 7.0 | — | — | — | — | — | — | ||||||||
| 10 | 4.5 | 2.7 | 2.0 | 78.5 | 1.3 | 10.0 | 93.0 | 0.9 | 6.0 | — | — | — | ||||||||
| 20 | 1.5 | 4.9 | 0 | 77.5 | 2.1 | 9.0 | — | — | — | — | — | — | ||||||||
| 20 | 8.0 | 3.7 | 4.0 | 75.5 | 3.7 | 4.0 | — | — | — | — | — | — | ||||||||
| 20 | 8.5 | 2.6 | 1.0 | 72.0 | 3.7 | 5.0 | — | — | — | — | — | — | ||||||||
| 30 | 5.5 | 3.3 | 0.4 | 67.5 | 2.6 | 6.0 | 97.0 | 3.5 | 3.0 | — | — | — | ||||||||
| 30 | 8.0 | 3.2 | 1.0 | 82.5 | 3.5 | 6.0 | — | — | — | — | — | — | ||||||||
| 30 | 21.5 | 3.4 | 2.0 | — | — | — | — | — | — | — | — | — | ||||||||
| B - lipo, % | ||||||||||||||||||||
| 5 | 0.1 | 0.5 | 0 | 0.6 | 0 | 0 | 1.0 | 0.3 | 26.0 | 22.0 | 0 | 4.0 | ||||||||
| 5 | 0 | 0 | 0 | 0.6 | 1.0 | 0 | 0.3 | 0 | 0 | 0.3 | 12.3 | 7.0 | ||||||||
| 5 | 0.1 | 0 | 0 | 4.5 | 1.4 | 10.0 | 0 | 0 | 0 | 0 | 0 | 0 | ||||||||
| 10 | 0.1 | 0 | 0 | 5.5 | 0.5 | 0 | 17.5 | 0.4 | 17.0 | 62.5 | 1.3 | 14.0 | ||||||||
| 10 | 0.2 | 2.0 | 0 | 16.5 | 0.7 | 8.0 | 80.5 | 0.1 | 25.0 | — | — | — | ||||||||
| 10 | 0.1 | 0 | 0 | 23.0 | 0.5 | 15.0 | — | — | — | — | — | — | ||||||||
| 20 | 0.7 | 7.6 | 0 | 83.0 | 0.9 | 13.0 | — | — | — | — | — | — | ||||||||
| 20 | 0.1 | 1.0 | 0 | 0.6 | 0.8 | 0 | 3.0 | 0.3 | 16.0 | 30.0 | 0.5 | 18.0 | ||||||||
| 20 | 0 | 0 | 0 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0.7 | 1.6 | 7.0 | ||||||||
| 30 | 0.4 | 3.9 | 0.6 | 57.5 | 0.5 | 17.0 | — | — | — | — | — | — | ||||||||
| 30 | 0.3 | 4.4 | 0 | 38.5 | 0.3 | 24.0 | 33.0 | 0.2 | 12.0 | — | — | — | ||||||||
| 30 | 0.6 | 0 | 0 | 5.0 | 1.0 | 15.0 | 48.0 | 0.2 | 14.0 | — | — | — | ||||||||
. | Day 7 . | . | . | Day 14 . | . | . | Day 21 . | . | . | Day 62 . | . | . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PBMCs, × 106 . | hCD45 . | CD4/CD8 . | CD4+CD8+ . | hCD45 . | CD4/CD8 . | CD4+CD8+ . | hCD45 . | CD4/CD8 . | CD4+CD8+ . | hCD45 . | CD4/CD8 . | CD4+CD8+ . | ||||||||
| A + lipo, % | ||||||||||||||||||||
| 5 | 3.5 | 4.1 | 0 | 42.0 | ND | 5.0 | 61.5 | 0.1 | 8.0 | 3.5 | 1.3 | 4.0 | ||||||||
| 5 | 0.3 | 2.4 | 0 | 24.0 | 0.4 | 20.0 | 19.0 | 0.1 | 13.0 | 0.8 | 0 | 25.0 | ||||||||
| 5 | 0.3 | 6.3 | 0 | 35.0 | 1.2 | 9.0 | 83.0 | 0.8 | 5.0 | — | — | — | ||||||||
| 10 | 5.0 | 1.9 | 1.0 | 70.5 | 2.7 | 5.0 | — | — | — | — | — | — | ||||||||
| 10 | 6.0 | 2.2 | 0.3 | 77.5 | 1.5 | 7.0 | — | — | — | — | — | — | ||||||||
| 10 | 4.5 | 2.7 | 2.0 | 78.5 | 1.3 | 10.0 | 93.0 | 0.9 | 6.0 | — | — | — | ||||||||
| 20 | 1.5 | 4.9 | 0 | 77.5 | 2.1 | 9.0 | — | — | — | — | — | — | ||||||||
| 20 | 8.0 | 3.7 | 4.0 | 75.5 | 3.7 | 4.0 | — | — | — | — | — | — | ||||||||
| 20 | 8.5 | 2.6 | 1.0 | 72.0 | 3.7 | 5.0 | — | — | — | — | — | — | ||||||||
| 30 | 5.5 | 3.3 | 0.4 | 67.5 | 2.6 | 6.0 | 97.0 | 3.5 | 3.0 | — | — | — | ||||||||
| 30 | 8.0 | 3.2 | 1.0 | 82.5 | 3.5 | 6.0 | — | — | — | — | — | — | ||||||||
| 30 | 21.5 | 3.4 | 2.0 | — | — | — | — | — | — | — | — | — | ||||||||
| B - lipo, % | ||||||||||||||||||||
| 5 | 0.1 | 0.5 | 0 | 0.6 | 0 | 0 | 1.0 | 0.3 | 26.0 | 22.0 | 0 | 4.0 | ||||||||
| 5 | 0 | 0 | 0 | 0.6 | 1.0 | 0 | 0.3 | 0 | 0 | 0.3 | 12.3 | 7.0 | ||||||||
| 5 | 0.1 | 0 | 0 | 4.5 | 1.4 | 10.0 | 0 | 0 | 0 | 0 | 0 | 0 | ||||||||
| 10 | 0.1 | 0 | 0 | 5.5 | 0.5 | 0 | 17.5 | 0.4 | 17.0 | 62.5 | 1.3 | 14.0 | ||||||||
| 10 | 0.2 | 2.0 | 0 | 16.5 | 0.7 | 8.0 | 80.5 | 0.1 | 25.0 | — | — | — | ||||||||
| 10 | 0.1 | 0 | 0 | 23.0 | 0.5 | 15.0 | — | — | — | — | — | — | ||||||||
| 20 | 0.7 | 7.6 | 0 | 83.0 | 0.9 | 13.0 | — | — | — | — | — | — | ||||||||
| 20 | 0.1 | 1.0 | 0 | 0.6 | 0.8 | 0 | 3.0 | 0.3 | 16.0 | 30.0 | 0.5 | 18.0 | ||||||||
| 20 | 0 | 0 | 0 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0.7 | 1.6 | 7.0 | ||||||||
| 30 | 0.4 | 3.9 | 0.6 | 57.5 | 0.5 | 17.0 | — | — | — | — | — | — | ||||||||
| 30 | 0.3 | 4.4 | 0 | 38.5 | 0.3 | 24.0 | 33.0 | 0.2 | 12.0 | — | — | — | ||||||||
| 30 | 0.6 | 0 | 0 | 5.0 | 1.0 | 15.0 | 48.0 | 0.2 | 14.0 | — | — | — | ||||||||
In group A, macrophage depletion was performed using clodronate-containing liposomes (+ lipo). Groups A and B received huPBMC doses of 5, 10, 20, and 30 × 106. Engraftment rates of human cells (hCD45) as a fraction of total (mouse + human) CD45+ cells, CD4/CD8 ratios, and fractions of CD4+/CD8+ cells in peripheral blood are shown.
Lipo indicates liposomes.; —, death of mice without further data; and ND, no data/sample error.