Combination of anti-CD28 mAb and rapamycin leads to long-term donor T- and B-cell reconstitution
. | . | Donor T cells . | . | . | Donor B cells . | . | . | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
. | Survival, % . | % . | ×106 . | cpm × 1000 . | % . | ×106 . | cpm × 1000 . | ||||
BM alone | 100 | 18 ± 3 | 22 ± 5 | 11 ± 2 | 60 ± 4 | 73 ± 10 | 53 ± 11 | ||||
Control | 0 | — | — | — | — | — | — | ||||
Rapamycin | 0 | — | — | — | — | — | — | ||||
αCD28 | 40 | 25 ± 3* | 4 ± 1† | 5 ± 2† | 25 ± 10† | 4 ± 2† | 34 ± 7† | ||||
αCD28 + rapamycin | 57 | 23 ± 2* | 13 ± 7† | 9 ± 2* | 62 ± 7* | 35 ± 5† | 56 ± 13* |
. | . | Donor T cells . | . | . | Donor B cells . | . | . | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
. | Survival, % . | % . | ×106 . | cpm × 1000 . | % . | ×106 . | cpm × 1000 . | ||||
BM alone | 100 | 18 ± 3 | 22 ± 5 | 11 ± 2 | 60 ± 4 | 73 ± 10 | 53 ± 11 | ||||
Control | 0 | — | — | — | — | — | — | ||||
Rapamycin | 0 | — | — | — | — | — | — | ||||
αCD28 | 40 | 25 ± 3* | 4 ± 1† | 5 ± 2† | 25 ± 10† | 4 ± 2† | 34 ± 7† | ||||
αCD28 + rapamycin | 57 | 23 ± 2* | 13 ± 7† | 9 ± 2* | 62 ± 7* | 35 ± 5† | 56 ± 13* |
Lethally irradiated (1200 cGy) B10.BR recipients were given transplants of 15 × 106 T-cell-depleted marrow cells plus 25 × 106 splenocytes from C57BL/6 donors. Recipients were treated intraperitoneally with either anti-CD28 mAb (αCD28) at 100 μg × 1 or rapamycin (rapamycin) at 1.5 mg/kg × 14 days or both (αCD28 + rapamycin). Surviving recipients were killed on day 120 after transplantation. Splenocytes were stained for expression of CD4, CD8, B220 and H2Kb. T-cell function was measured by stimulating splenocytes with Concanavalin A for 3 days, and B cell function was measured by stimulating splenocytes with LPS for 3 days. Data are presented as average counts per minute (cpm) ± SD. Results are representative of 2 replicate experiments. — indicates that no data are available, because all mice in this group died before day 120.
P > .05 compared with BM alone
P < .05 compared with BM alone