Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells
Table 3
Statistical analysis of histology and immunohistochemistry data in macrophage depletion. Mean survival with Standard Deviation (SD) values for histological and immunohistochemical scoring in macrophage-depletion experiments 1 and 2, each experiment comparing mice injected with huPBMCs with macrophage depletion by clodronate-containing liposome injection (liposomes+) and mice injected with huPBMCs without clodronate-containing liposome injection (liposomes-). The encountered effect related to liposomes injected is indicated with arrows indicating an associated increase or decrease of the mean histological infiltration scores.
Fibrosis
T-cells
B-cells (CD79a)
B-cells (CD20)
Plasma cells
Tregs
N (+/- liposomes)
Effect of liposomes
value
Significant
Effect of liposomes
value
Significant
Effect of liposomes
value
Significant
Effect of liposomes
value
Significant
Effect of liposomes
value
Significant
Effect of liposomes
value
Significant
Spleen
Exp. 1
Single donor
10(3/7)
↓
0.22
No
↓
0.22
No
↓
0.11
No
↑
0.11
No
↓
0.68
No
↑
0.21
No
Exp. 2
Pooled data (donor A+B)
16 (8/8)
↑
0.28
No
↑
0.16
No
↑
<0.0001
Yes
↑
<0.0001
Yes
↑
0.0008
Yes
#
#
Donor A only
9 (5/4)
↓
0.0035
Yes
↓
0.1131
No
↑
<0.0001
Yes
↑
0.0314
Yes
↑
<0.0001
Yes
#
#
Donor B only
7 (3/4)
↑
0.5514
No
↑
0.0321
Yes
↑
0.0013
Yes
↑
0.5857
No
↑
0.2112
No
#
#
Liver
Exp. 1
Single donor
10(3/7)
↓
0.06
No
↓
0.11
No
↓
0.04
Yes
↑
0.01
Yes
↓
0.48
No
↑
0.17
No
Exp. 2
Pooled data (donor A+B)
16 (8/8)
↑
0.1
No
↑
0.0006
Yes
↑
0.002
Yes
↑
0.002
Yes
↑
0.0003
Yes
#
#
Donor A only
9 (5/4)
↑
0.0031
Yes
↑
0.0001
Yes
↑
0.0005
Yes
↑
0.0431
Yes
↑
0.006
Yes
#
#
Donor B only
7 (3/4)
↓
0.6447
No
↑
0.3743
No
↓
0.4178
No
↑
0.2367
No
↑
0.0101
Yes
#
#
Lung
Exp. 1
Single donor
10(3/7)
↓
0.21
No
↓
0.31
No
↓
0.06
No
↑
0.04
Yes
↓
0.06
No
↑
0.1
No
Exp. 2
Pooled data (donor A+B)
16 (8/8)
↓
0.25
No
↑
0.01
Yes
↑
0.028
Yes
↑
0.028
Yes
↑
0.0004
Yes
#
#
Donor A only
9 (5/4)
≈
0.393
No
↑
0.05
Yes
↑
0.4231
No
↑
0.1094
No
↑
0.0202
Yes
#
#
Donor B only
7 (3/4)
↓
0.5206
No
↑
0.69
No
↑
0.0033
No
↑
0.8255
No
↑
0.0007
Yes
#
#
Skin
Exp. 1
Single donor
10(3/7)
≈
1
No
↓
0.27
No
↓
0.11
No
#
#
↓
0.22
No
≈
1.00
No
Exp. 2
Pooled data (donor A+B)
16 (8/8)
≈
0.35
No
↑
0.0044
Yes
↑
0.0237
Yes
↑
0.0237
Yes
↑
0.548
No
#
#
Donor A only
9 (5/4)
↑
0.23
No
↑
0.036
Yes
↑
0.013
Yes
#
#
↓
0.3927
No
#
#
Donor B only
7 (3/4)
≈
0.71
No
↑
0.1097
No
#
#
#
#
#
#
#
#
Colon
Exp. 1
Single donor
10(3/7)
#
#
≈
0.89
No
#
#
#
#
#
#
↑
0.72
No
Exp. 2
Pooled data (donor A+B)
16 (8/8)
↑
0.792
No
↑
0.0137
Yes
↑
0.88
No
#
#
≈
0.486
No
#
#
Donor A only
9 (5/4)
≈
0.9438
No
↑
0.018
Yes
↑
0.5669
No
#
#
↑
0.3342
No
#
#
Donor B only
7 (3/4)
↑
0.7439
No
↑
0.5864
No
↓
0.4178
No
#
#
↓
0.4178
No
#
#
Femur
Exp. 1
Single donor
10(3/7)
↑
0.68
No
↑
0.59
No
↑
0.89
No
↑
0.01
Yes
↑
0.04
Yes
↑
0.46
N o
Exp. 2
Pooled data (donor A+B)
16 (8/8)
↑
0.0005
Yes
↑
0.0001
Yes
↑
0.0534
No
↑
0.0534
No
↑
0.253
No
#
#
Donor A only
9 (5/4)
↑
0.0075
Yes
↑
0.0012
Yes
↑
0.0057
Yes
↑
0.1074
No
↑
0.553
No
#
#
Donor B only
7 (3/4)
↑
0.076
No
↑
0.1251
No
↑
1.00
No
↑
!
!
↑
0.3165
No
#
#
#: no cells/fibrosis detected, significant difference between scoring of the analysts, morphologically plasma cells with CD79a staining, !: number of available data not sufficient for analysis, ↑: mean score liposomes > mean score without liposomes, ↓: mean score liposomes < mean score without liposomes, ≈: mean scores almost equal.
