IL-7 administration enhances T- and B-cell reconstitution after allogeneic BMT
| . | Phenotype . | B10.BR → CBA (3 mo) . | B10.BR → CBA (9 mo) . | B6 → (B6 × C3H)F1 . | |||
|---|---|---|---|---|---|---|---|
| PBS . | IL-7 . | PBS . | IL-7 . | PBS . | IL-7 . | ||
| Thymocytes | |||||||
| Total number | 46.1 ± 7.1 | 80.7 ± 8.7 | 13.7 ± 2.2 | 31.0 ± 4.7 | 50.4 ± 5.8 | 75.3 ± 7.7 | |
| DN1 | CD44+ CD25−CD3− CD4−CD8− | 0.15 ± .06 | 0.23 ± .06 | .07 ± .01 | 0.1 ± .01 | 0.3 ± .03 | 0.8 ± 0.2 |
| DN2 | CD44+ CD25+ CD3−CD4−CD8− | 0.07 ± .03 | 0.07 ± .02 | .07 ± .03 | 0.04 ± .01 | 0.2 ± .02 | 0.2 ± .02 |
| DN3 | CD44− CD25+ CD3−CD4−CD8− | 0.4 ± .09 | 0.9 ± 0.1 | .07 ± .02 | 0.2 ± .05 | 0.6 ± 0.1 | 1.0 ± .06 |
| DP | CD4+CD8+ | 32.5 ± 5.2 | 65.9 ± 7.1 | 11.5 ± 1.9 | 27.0 ± 2.5 | 37.8 ± 4.7 | 55.4 ± 5.8 |
| CD4+ SP | CD4+CD8− | 3.6 ± .06 | 7.2 ± 0.9 | 1.2 ± 0.2 | 2.3 ± 0.3 | 7.8 ± 0.9 | 11.9 ± 0.3 |
| CD8+ SP | CD4−CD8+ | 1.5 ± 0.3 | 3.0 ± 0.4 | 0.4 ± .05 | 1.0 ± 1.1 | 2.1 ± 0.3 | 2.9 ± 0.2 |
| T cells (spleen) | |||||||
| T cells (donor) | CD3+Ly9.1− | 9.3 ± 2.5 | 20.7 ± 3.0 | 10.8 ± 1.6 | 20.6 ± 1.6 | 9.0 ± 1.0 | 22.4 ± 2.8 |
| T cells (host) | CD3+Ly9.1+ | 3.1 ± 0.4 | 5.0 ± 0.8 | 2.8 ± 0.6 | 4.2 ± 1.2 | 6.1 ± 0.6 | 18.7 ± 2.5 |
| Naive CD4+ | CD4+ CD44 (lo) CD62L (hi) | 0.6 ± 0.1 | 1.9 ± 0.3 | 0.8 ± 0.2 | 1.1 ± 0.2 | 4.2 ± 0.6 | 7.5 ± 0.8 |
| Activated CD4+ | CD4+ CD44 (hi) CD62L (hi) | 1.6 ± 0.3 | 4.4 ± 0.5 | 3.2 ± 0.4 | 5.9 ± 0.3 | 1.8 ± 0.2 | 4.8 ± 0.3 |
| Memory CD4+ | CD4+ CD44 (hi) CD62L (lo) | 6.2 ± 0.8 | 16.3 ± 1.0 | 5.8 ± 0.8 | 9.7 ± 0.7 | 3.7 ± 0.2 | 10.0 ± 0.6 |
| Naive CD8+ | CD8+ CD44 (lo) | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.3 ± 0.1 | 0.4 ± 0.1 | 1.2 ± 0.1 | 2.5 ± 0.2 |
| Act/Mem CD8+ | CD8+ CD44 (hi) | 2.7 ± 0.0 | 5.2 ± 0.8 | 6.1 ± 0.8 | 9.8 ± 0.7 | 2.2 ± 0.2 | 7.9 ± 0.8 |
| B cells | |||||||
| Pro-B (BM) | CD43+ CD45R+IgM− | 0.3 ± .05 | 0.8 ± 0.1 | 0.9 ± 0.2 | 3.3 ± 0.4 | 0.6 ± .06 | 0.7 ± 0.1 |
| Pre-B (BM) | CD43− CD45R+IgM− | 1.2 ± 0.3 | 5.0 ± 0.6 | 3.6 ± 0.6 | 10.7 ± 2.6 | 3.5 ± 0.3 | 9.5 ± 1.3 |
| Immature B (BM) | CD43− CD45R+IgM+ | 1.0 ± 0.2 | 1.9 ± 0.4 | 5.8 ± 1.0 | 10.7 ± 1.5 | 1.4 ± 0.1 | 2.7 ± 0.4 |
| Pro-B (spleen) | CD43+ CD45R+IgM− | 1.7 ± 0.6 | 14.6 ± 2.6 | 2.1 ± 0.3 | 12.9 ± 2.9 | 1.1 ± .09 | 4.8 ± 0.5 |
| Pre-B (spleen) | CD43− CD45R+IgM− | 3.9 ± 0.9 | 33.4 ± 3.8 | 10.4 ± 1.9 | 40.4 ± 4.3 | 2.9 ± 0.4 | 33.5 ± 5.1 |
| Immature B (spleen) | CD43− CD45R+IgM+ | 58.8 ± 8.0 | 108.0 ± 6.0 | 59.4 ± 11 | 122.6 ± 16 | 42.2 ± 5.2 | 122.5 ± 13 |
| CD19+ (donor) | CD19+Ly9.1− | 81.9 ± 13 | 186.0 ± 14 | 119.5 ± 9.3 | 233.2 ± 24 | 50.0 ± 5.3 | 169.6 ± 19 |
| CD19+ (host) | CD19+Ly9.1+ | 2.8 ± .05 | 4.6 ± 0.4 | 4.4 ± 0.5 | 7.4 ± 1.2 | 3.7 ± 0.4 | 11.6 ± 0.8 |
| Macrophages (spleen) | |||||||
| CD11b (donor) | CD11b+Ly9.1− | 8.3 ± 1.3 | 15.5 ± 2.0 | 36.8 ± 4.7 | 74.9 ± 6.0 | 8.9 ± 0.8 | 26.7 ± 1.5 |
| CD11b (host) | CD11b+Ly9.1+ | 0.8 ± 0.2 | 0.7 ± 0.1 | 2.9 ± 0.5 | 4.5 ± 0.7 | 2.2 ± 0.3 | 5.8 ± 0.6 |
| NK and NK T cells (spleen) | |||||||
| NK1.1 (donor) | NK1.1+Ly9.1− | 5.5 ± 1.2 | 11.3 ± 1.8 | 2.2 ± 0.2 | 3.6 ± 0.4 | 2.3 ± 0.3 | 5.2 ± 0.7 |
| NK1.1 (host) | NK1.1+Ly9.1+ | 1.9 ± 0.4 | 2.8 ± 0.8 | 0.6 ± 0.1 | 1.5 ± 0.3 | 0.9 ± .10 | 2.8 ± 0.3 |
| NK T | TCRαβ+NK1.1+ | 3.8 ± 0.5 | 3.0 ± 1.0 | 1.2 ± 0.2 | 2.2 ± 0.4 | 0.7 ± 0.1 | 2.8 ± 0.3 |
| Peripheral blood | |||||||
| WBCs | 3.3 ± .40 | 6.5 ± 0.6 | 2.2 ± .20 | 3.5 ± 0.2 | 4.0 ± 0.4 | 6.1 ± 1.0 | |
| Lymph | 2.5 ± 0.4 | 5.3 ± 0.6 | 1.3 ± 0.2 | 2.4 ± 0.1 | 2.7 ± 0.4 | 4.5 ± 0.7 | |
| . | Phenotype . | B10.BR → CBA (3 mo) . | B10.BR → CBA (9 mo) . | B6 → (B6 × C3H)F1 . | |||
|---|---|---|---|---|---|---|---|
| PBS . | IL-7 . | PBS . | IL-7 . | PBS . | IL-7 . | ||
| Thymocytes | |||||||
| Total number | 46.1 ± 7.1 | 80.7 ± 8.7 | 13.7 ± 2.2 | 31.0 ± 4.7 | 50.4 ± 5.8 | 75.3 ± 7.7 | |
| DN1 | CD44+ CD25−CD3− CD4−CD8− | 0.15 ± .06 | 0.23 ± .06 | .07 ± .01 | 0.1 ± .01 | 0.3 ± .03 | 0.8 ± 0.2 |
| DN2 | CD44+ CD25+ CD3−CD4−CD8− | 0.07 ± .03 | 0.07 ± .02 | .07 ± .03 | 0.04 ± .01 | 0.2 ± .02 | 0.2 ± .02 |
| DN3 | CD44− CD25+ CD3−CD4−CD8− | 0.4 ± .09 | 0.9 ± 0.1 | .07 ± .02 | 0.2 ± .05 | 0.6 ± 0.1 | 1.0 ± .06 |
| DP | CD4+CD8+ | 32.5 ± 5.2 | 65.9 ± 7.1 | 11.5 ± 1.9 | 27.0 ± 2.5 | 37.8 ± 4.7 | 55.4 ± 5.8 |
| CD4+ SP | CD4+CD8− | 3.6 ± .06 | 7.2 ± 0.9 | 1.2 ± 0.2 | 2.3 ± 0.3 | 7.8 ± 0.9 | 11.9 ± 0.3 |
| CD8+ SP | CD4−CD8+ | 1.5 ± 0.3 | 3.0 ± 0.4 | 0.4 ± .05 | 1.0 ± 1.1 | 2.1 ± 0.3 | 2.9 ± 0.2 |
| T cells (spleen) | |||||||
| T cells (donor) | CD3+Ly9.1− | 9.3 ± 2.5 | 20.7 ± 3.0 | 10.8 ± 1.6 | 20.6 ± 1.6 | 9.0 ± 1.0 | 22.4 ± 2.8 |
| T cells (host) | CD3+Ly9.1+ | 3.1 ± 0.4 | 5.0 ± 0.8 | 2.8 ± 0.6 | 4.2 ± 1.2 | 6.1 ± 0.6 | 18.7 ± 2.5 |
| Naive CD4+ | CD4+ CD44 (lo) CD62L (hi) | 0.6 ± 0.1 | 1.9 ± 0.3 | 0.8 ± 0.2 | 1.1 ± 0.2 | 4.2 ± 0.6 | 7.5 ± 0.8 |
| Activated CD4+ | CD4+ CD44 (hi) CD62L (hi) | 1.6 ± 0.3 | 4.4 ± 0.5 | 3.2 ± 0.4 | 5.9 ± 0.3 | 1.8 ± 0.2 | 4.8 ± 0.3 |
| Memory CD4+ | CD4+ CD44 (hi) CD62L (lo) | 6.2 ± 0.8 | 16.3 ± 1.0 | 5.8 ± 0.8 | 9.7 ± 0.7 | 3.7 ± 0.2 | 10.0 ± 0.6 |
| Naive CD8+ | CD8+ CD44 (lo) | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.3 ± 0.1 | 0.4 ± 0.1 | 1.2 ± 0.1 | 2.5 ± 0.2 |
| Act/Mem CD8+ | CD8+ CD44 (hi) | 2.7 ± 0.0 | 5.2 ± 0.8 | 6.1 ± 0.8 | 9.8 ± 0.7 | 2.2 ± 0.2 | 7.9 ± 0.8 |
| B cells | |||||||
| Pro-B (BM) | CD43+ CD45R+IgM− | 0.3 ± .05 | 0.8 ± 0.1 | 0.9 ± 0.2 | 3.3 ± 0.4 | 0.6 ± .06 | 0.7 ± 0.1 |
| Pre-B (BM) | CD43− CD45R+IgM− | 1.2 ± 0.3 | 5.0 ± 0.6 | 3.6 ± 0.6 | 10.7 ± 2.6 | 3.5 ± 0.3 | 9.5 ± 1.3 |
| Immature B (BM) | CD43− CD45R+IgM+ | 1.0 ± 0.2 | 1.9 ± 0.4 | 5.8 ± 1.0 | 10.7 ± 1.5 | 1.4 ± 0.1 | 2.7 ± 0.4 |
| Pro-B (spleen) | CD43+ CD45R+IgM− | 1.7 ± 0.6 | 14.6 ± 2.6 | 2.1 ± 0.3 | 12.9 ± 2.9 | 1.1 ± .09 | 4.8 ± 0.5 |
| Pre-B (spleen) | CD43− CD45R+IgM− | 3.9 ± 0.9 | 33.4 ± 3.8 | 10.4 ± 1.9 | 40.4 ± 4.3 | 2.9 ± 0.4 | 33.5 ± 5.1 |
| Immature B (spleen) | CD43− CD45R+IgM+ | 58.8 ± 8.0 | 108.0 ± 6.0 | 59.4 ± 11 | 122.6 ± 16 | 42.2 ± 5.2 | 122.5 ± 13 |
| CD19+ (donor) | CD19+Ly9.1− | 81.9 ± 13 | 186.0 ± 14 | 119.5 ± 9.3 | 233.2 ± 24 | 50.0 ± 5.3 | 169.6 ± 19 |
| CD19+ (host) | CD19+Ly9.1+ | 2.8 ± .05 | 4.6 ± 0.4 | 4.4 ± 0.5 | 7.4 ± 1.2 | 3.7 ± 0.4 | 11.6 ± 0.8 |
| Macrophages (spleen) | |||||||
| CD11b (donor) | CD11b+Ly9.1− | 8.3 ± 1.3 | 15.5 ± 2.0 | 36.8 ± 4.7 | 74.9 ± 6.0 | 8.9 ± 0.8 | 26.7 ± 1.5 |
| CD11b (host) | CD11b+Ly9.1+ | 0.8 ± 0.2 | 0.7 ± 0.1 | 2.9 ± 0.5 | 4.5 ± 0.7 | 2.2 ± 0.3 | 5.8 ± 0.6 |
| NK and NK T cells (spleen) | |||||||
| NK1.1 (donor) | NK1.1+Ly9.1− | 5.5 ± 1.2 | 11.3 ± 1.8 | 2.2 ± 0.2 | 3.6 ± 0.4 | 2.3 ± 0.3 | 5.2 ± 0.7 |
| NK1.1 (host) | NK1.1+Ly9.1+ | 1.9 ± 0.4 | 2.8 ± 0.8 | 0.6 ± 0.1 | 1.5 ± 0.3 | 0.9 ± .10 | 2.8 ± 0.3 |
| NK T | TCRαβ+NK1.1+ | 3.8 ± 0.5 | 3.0 ± 1.0 | 1.2 ± 0.2 | 2.2 ± 0.4 | 0.7 ± 0.1 | 2.8 ± 0.3 |
| Peripheral blood | |||||||
| WBCs | 3.3 ± .40 | 6.5 ± 0.6 | 2.2 ± .20 | 3.5 ± 0.2 | 4.0 ± 0.4 | 6.1 ± 1.0 | |
| Lymph | 2.5 ± 0.4 | 5.3 ± 0.6 | 1.3 ± 0.2 | 2.4 ± 0.1 | 2.7 ± 0.4 | 4.5 ± 0.7 | |
Lethally irradiated (1300 cGy) CBA/J recipients (3 and 9 months old) received transplants with B10.BR TCD BM (5 × 106) and lethally irradiated (1300 cGy) (B6 × C3H)F1 recipients received B6 TCD BM (5 × 106). Recipients received 10 μg/d IL-7 or PBS (control) by intraperitoneal injection from day 21 to day 27. Animals were humanely killed on day 28 and populations of cells were calculated from total cell counts and multicolor flow cytometric analyses. Donor or host origin was determined with anti-Ly9.1 or anti-CD5.1, which only reacts with leukocytes of host origin. Absolute lymphocyte counts were calculated from automated complete blood counts and differential counts on a blood smear. Values represent mean cell number (106) ± SE and each group contained 6 to 8 animals. All values in bold represent significantly increased cell numbers (P < .05) in IL-7–treated recipients compared to PBS-treated control recipients. Peripheral blood values represent cell count × 103/μL ± SE. DN indicates double-negative thymocytes; DP, double-positive thymocytes, SP, single-positive thymocytes; Act/Mem, activated + memory cells; WBCs, white blood cells; Lymph, lymphocytes.