Table I.
Cell subsets important in mediating the effects of LPS on the establishment if hematopoietic chimerism in mice treated with costimulation blockadea
Group | Host | LPS | Anti-NK | Anti-CD8 | Anti-CD4 | Chimerism Frequency | Donor-Origin PBMCs at 8 wk (%) | MST of Skin Grafts in Transplanted Mice (days) | MST of Skin Grafts in Nonchimeric Mice (days) | MST of Skin Grafts in Chimeric Mice (days) |
---|---|---|---|---|---|---|---|---|---|---|
1 | C57BL/6 | No | No | No | No | 29/45 (64%) | 1.59 ± 1.81 | 144 | 88 | >260 |
2 | C57BL/6 | Yes | No | No | No | 0/23 (0%)b | <0.10 | 11* | 11 | N/A |
3 | C57BL/6 | No | Yes | No | No | 11/13 (84.6%) | 2.45 ± 1.16 | >221 | 72 | >221 |
4 | C57BL/6 | Yes | Yes | No | No | 0/5 (<0.10%)c | <0.10 | 12** | 12 | N/A |
5 | C57BL/6 | No | No | Yes | No | 15/17 (88.2%) | 0.90 ± 1.13 | 144 | 72.5 | 148 |
6 | C57BL/6 | Yes | No | Yes | No | 0/16 (<0.10%)d | <0.10 | 44# | 44 | N/A |
7 | C57BL/6 | No | Yes | Yes | No | 7/8 (87.5%) | 3.67 ± 1.23 | 81 | 23 | 81 |
8 | C57BL/6 | Yes | Yes | Yes | No | 0/9 (<0.10%)e | <0.10 | 28## | 28 | N/A |
9 | C57BL/6 | No | No | No | Yes | 1/12 (8.33%) | 0.58 | 46 | 37 | >147 |
10 | C57BL/6 | Yes | No | No | Yes | 0/12 (<0.10%)f | <0.10 | 18 | 18 | N/A |
11 | C57BL/6 | No | No | Yes | Yes | 4/4 (100%) | 2.42 ± 0.55 | >228 | N/A | >228 |
12 | C57BL/6 | Yes | No | Yes | Yes | 4/4 (100%)g | 1.14 ± 0.35 | 228 | N/A | 228 |
13 | CD8α−/− | No | No | No | No | 12/17 (70.5%) | 2.29 ± 1.76 | 96 | 51 | 136 |
14 | CD8α−/− | Yes | No | No | No | 0/17 (<0.10%)h | <0.10 | 21$ | 21 | N/A |
All mice were treated with a BALB/c DST and anti-CD154 mAb and transplanted with BALB/c bone marrow and skin according to our standard protocol without or with injection of 100 µg of LPS. Groups 3, 4, 7, and 8 were also given an injection of anti-NK1.1 mAb i.p on day −10 relative to bone marrow and skin transplantation. Groups 5, 6, 7, 8, 11, and 12 were given three doses of 0.5 mg of anti-CD8 mAb i.p. on days −10, −9, and −8 relative to bone marrow and skin transplantation. Groups 9, 10, 11, and 12 were given three doses of 0.5 mg of anti-CD4 mAb i.p. on days −10, −9, and −8 relative to bone marrow and skin transplantation. Hematopoietic chimerism was defined as >0.10% donor origin PBMCs 8 wk after bone marrow injection. The percentage of donor origin PBMCs is the mean ± SD percentage of the levels observed in chimeric mice. For groups with no chimeric mice, we used the limit of detection (<0.10) to indicate a lack of chimerism.
p = 0.017 vs group 1
p = 0.0005 vs group 3
p < 0.0001 vs group 5
p = 0.0003 vs group 7
p = NS vs group 9
p = NS vs group 11
p < 0.0001 vs group 13 by χ2 analysis.
p < 0.001 vs group 1
p < 0.0001 vs group 3
p < 0.0001 vs group 5
p < 0.01 vs group 7
p < 0.001 vs group 13 by log-rank analysis.
N/A, Not applicable.