Table 3.
Expression levels of 78 genes constituting multiple immune gene networks that were striking up-regulated by bacille Calmette-Guérin (BCG) vaccination/infection.
| Gene | Gene ratio for BCG |
Gene ratio for control |
||
|---|---|---|---|---|
| Mean ± SD | P | Mean ± SD | P | |
| IL-1α | 4.1 ± 6.5 | .490 | 0.3 ± 0.1 | .055 |
| IL-1β | 16.4 ± 26.5 | .097 | 1.9 ± 1.4 | .527 |
| IL-2 | UD | UD | UD | UD |
| IL-3 | 113.9 ± 107.0 | .028a | 1.0 ± 0.1 | .714 |
| IL-4 | 4.3 ± 5.9 | .178 | 1.5 ± 2.7 | .827 |
| IL-5 | 1.1 ± 1.6 | .171 | 1.6 ± 2.1 | .680 |
| IL-6 | 3.0 ± 3.3 | .413 | 1.4 ± 1.1 | .734 |
| IL-7 | 2.5 ± 4.7 | .185 | 1.0 ± 0.1 | .721 |
| IL-8 | 65.1 ± 66.2 | .040a | 1.0 ± 0.1 | .268 |
| IL-9 | UD | UD | UD | UD |
| IL-10 | 0.4 ± 0.4 | .134 | 1.6 ± 1.4 | .565 |
| IL-12α | 1.2 ± 1.6 | .178 | 1.0 ± 0.1 | .631 |
| IL-12β | 1.5 ± 1.6 | .197 | 2.7 ± 2.5 | .282 |
| IL-13 | 1.4 ± 1.7 | .209 | 0.3 ± 0.2 | .166 |
| IL-15 | 10.0 ± 9.5 | .029a | 1.1 ± 0.1 | .153 |
| IL-16 | 25.9 ± 22.7 | .004b | 2.3 ± 1.0 | .141 |
| IL-17 | 1.5 ± 1.5 | .216 | 1.0 ± 0.0 | .177 |
| IL-18 | 235.6 ± 335.7 | .037a | 1.0 ± 0.1 | .293 |
| IL-19 | UD | UD | UD | UD |
| IL-20 | 27.1 ± 30.2 | .001b | 1.1 ± 0.1 | .239 |
| IL-21 | 4.3 ± 5.4 | .456 | 1.1 ± 0.1 | .268 |
| IL-22 | 115.1 ± 114.8 | .005b | 2.5 ± 3.6 | .930 |
| IL-23α | 11.4 ± 7.0 | .002b | 0.9 ± 0.5 | .648 |
| IL-27 | 8.2 ± 10.8 | .027a | UD | UD |
| IFN-α | 96.3 ± 94.6 | .001b | 0.9 ± 0.2 | .790 |
| IFN-β | 66.0 ± 67.5 | .000b | UD | UD |
| IFN-γ | 38.4 ± 37.7 | .000b | 1.8 ± 0.8 | .280 |
| MIF | 20.5 ± 23.0 | .006b | 0.9 ± 0.1 | .100 |
| TNF-α | 8.1 ± 5.1 | .030a | 1.8 ± 2.2 | .568 |
| IL-1R1 | 12.9 ± 18.7 | .123 | 0.9 ± 0.4 | .544 |
| IL-1R2 | 1.8 ± 1.8 | .323 | UD | UD |
| IL-2Rα | 8.5 ± 6.9 | .129 | 0.9 ± 0.1 | .146 |
| IL-2Rβ | 34.1 ± 29.3 | .001b | 2.3 ± 2.0 | .139 |
| IL-2Rγ | 39.7 ± 55.6 | .070 | 1.0 ± 0.2 | .631 |
| IL-3Rα | 44.7 ± 44.9 | .001b | UD | UD |
| IL-4R | 16.8 ± 21.4 | .158 | 1.0 ± 0.1 | .593 |
| IL-5Rα | 1.4 ± 1.5 | .202 | 1.0 ± 0.2 | .478 |
| IL-6R | 247.5 ± 168.5 | .008b | 2.1 ± 1.6 | .342 |
| IL-7R | 25.6 ± 49.3 | .481 | 1.1 ± 0.2 | .805 |
| IL-8Rα | 73.0 ± 82.1 | .000b | UD | UD |
| IL-9R | 1.4 ± 1.4 | .238 | 1.4 ± 1.2 | .459 |
| IL-10Rα | 9.0 ± 12.5 | .124 | 0.5 ± 0.3 | .148 |
| IL-10Rβ | 5.0 ± 7.1 | .291 | 1.1 ± 0.1 | .147 |
| IL-11Rα | 40.5 ± 43.0 | .001b | 1.3 ± 1.0 | .982 |
| IL-12Rβ1 | 4.0 ± 2.8 | .179 | 1.8 ± 1.1 | .172 |
| IL-12Rβ2 | 2.8 ± 1.9 | .427 | 1.0 ± 0.1 | .897 |
| IL-13Rα1 | 119.6 ± 182.0 | .003b | 1.0 ± 0.1 | .683 |
| IL-15Rα | 3.0 ± 3.0 | .249 | 2.6 ± 2.6 | .135 |
| IL-17R | 19.5 ± 19.6 | .247 | 1.3 ± 0.4 | .503 |
| IL-18R1 | 134.0 ± 110.4 | .002b | 1.0 ± 0.0 | .977 |
| IL-21R | 5.6 ± 8.4 | .266 | 1.0 ± 0.1 | .682 |
| IFN-γR | 76.7 ± 75.8 | .001b | 3.2 ± 3.5 | .392 |
| TNFR | 18.5 ± 27.5 | .005b | UD | UD |
| CCL27 | 9.7 ± 10.1 | .004b | 1.5 ± 1.7 | .910 |
| CCL28 | 87.5 ± 133.4 | .003b | 1.8 ± 2.5 | .833 |
| CXCL11 | 1.6 ± 2.1 | .179 | 1.0 ± 0.0 | .956 |
| CXCL12 | 1.2 ± 1.5 | .181 | 1.0 ± 0.1 | .364 |
| EOTAXIN | UD | UD | 1.0 ± 0.1 | .787 |
| Eta-1 | 1.1 ± 1.2 | .178 | 1.0 ± 0.1 | .374 |
| FRA | 28.1 ± 41.8 | .001b | 1.0 ± 0.0 | .110 |
| GCP2 | 107.0 ± 155.1 | .002b | 1.2 ± 0.6 | .936 |
| IP-10 | 26.0 ± 22.3 | .430 | 2.7 ± 3.5 | .882 |
| LARC | 1.2 ± 1.5 | .149 | 1.0 ± 0.1 | .253 |
| MCP1 | 18.0 ± 7.4 | .003b | UD | UD |
| MCP2 | 21.9 ± 29.3 | .007b | 1.0 ± 0.1 | .566 |
| MCP3 | 2.1 ± 1.7 | .279 | 1.0 ± 0.1 | .475 |
| MCP4 | 1.7 ± 1.8 | .208 | 1.0 ± 0.1 | .241 |
| MDC | 15.3 ± 20.8 | .017b | UD | UD |
| MIP-1α | 3.4 ± 0.8 | .010b | 0.9 ± 0.1 | .183 |
| MIP-1β | 62.7 ± 49.0 | .123 | 1.0 ± 0.0 | .725 |
| MIP-3β | 1.2 ± 1.6 | .183 | 1.0 ± 0.1 | .307 |
| PARC | 10.8 ± 14.8 | .092 | 1.7 ± 2.1 | .807 |
| RANTES | 3.4 ± 0.8 | .010a | 1.0 ± 0.1 | .871 |
| TARC | 1.4 ± 1.6 | .216 | 1.0 ± 0.1 | .422 |
| TECK | 17.7 ± 23.5 | .001b | 1.7 ± 1.7 | .795 |
| CCR1 | 12.0 ± 5.5 | .000b | 1.4 ± 0.5 | .682 |
| CCR2 | 21.9 ± 20.6 | .003b | 1.7 ± 1.2 | .779 |
| CCR3 | 9.8 ± 4.3 | .001b | 1.9 ± 3.0 | .922 |
| CCR4 | 51.8 ± 51.7 | .141 | 1.1 ± 0.1 | .434 |
| CCR5 | 263.2 ± 459.1 | .019a | 2.8 ± 3.5 | .668 |
| CCR6 | 51.4 ± 89.6 | .008b | UD | UD |
| CCR7 | 5.7 ± 6.7 | .006b | 2.6 ± 2.4 | .082 |
| CCR8 | 37.7 ± 37.4 | .000b | 1.2 ± 1.4 | .939 |
| CCR9 | 49.4 ± 49.0 | .001b | 1.5 ± 2.0 | .926 |
| CCR10 | 45.2 ± 38.2 | .000b | UD | UD |
| CCR11 | 18.7 ± 29.6 | .002b | 3.8 ± 4.7 | .671 |
| CX3CR1 | 54.4 ± 47.3 | .000b | UD | UD |
| CXCR3 | 5.3 ± 4.5 | .022a | 1.3 ± 1.3 | .893 |
| CXCR4 | 10.1 ± 5.9 | .002b | 1.0 ± 0.2 | .276 |
| CXCR5 | 4.4 ± 6.2 | .336 | 1.7 ± 1.4 | .432 |
| CXCR6 | 17.5 ± 13.8 | .010a | 3.2 ± 2.3 | .136 |
| XCR1 | 26.5 ± 32.0 | .000b | 3.1 ± 4.6 | .945 |
| ANGPT | UD | UD | 1.0 ± 0.0 | .436 |
| FGF18 | 3.0 ± 3.6 | .311 | 0.9 ± 1.5 | .554 |
| FGF2 | UD | UD | 1.4 ± 1.3 | .873 |
| IGF1 | 1.5 ± 2.2 | .198 | 3.0 ± 4.8 | .842 |
| TGFα | 1.4 ± 1.5 | .211 | 2.7 ± 3.9 | .428 |
| TGFβ1 | 2.4 ± 2.4 | .329 | 3.5 ± 2.6 | .154 |
| VEGF | 90.8 ± 128.7 | .001b | 1.1 ± 0.1 | .225 |
| C-MAF | 127.6 ± 214.5 | .000b | UD | UD |
| GATA-3 | 16.8 ± 21.4 | .158 | UD | UD |
| PU.1 | 73.9 ± 70.6 | .010a | 1.7 ± 1.7 | .451 |
| SCM1 | 14.2 ± 11.2 | .001b | 0.7 ± 0.9 | .991 |
| T-bet | 14.9 ± 14.6 | .007b | 1.8 ± 1.4 | .855 |
| B7-1 | 11.5 ± 21.9 | .144 | 1.0 ± 0.1 | .494 |
| B7-2 | 272.8 ± 522.8 | .038a | 2.8 ± 3.1 | .735 |
| CD28 | 603.9 ± 945.1 | .003b | 0.7 ± 0.4 | .411 |
| CTLA4 | 12.2 ± 8.3 | .004b | 0.8 ± 0.7 | .602 |
| ICOS | 23.8 ± 35.3 | .093 | 1.0 ± 0.0 | .196 |
| ICOSL | 5.5 ± 6.5 | .177 | 0.7 ± 0.4 | .150 |
| CTSG | 9.4 ± 9.8 | .001b | 2.5 ± 2.9 | .412 |
| GZMA | 260.7 ± 306.5 | .021a | 2.3 ± 2.1 | .269 |
| GZMB | 30.0 ± 28.8 | .000b | UD | UD |
| GZMK | 104.0 ± 83.0 | .000b | 1.8 ± 1.0 | .292 |
| GZMM | 41.3 ± 45.0 | .001b | 0.9 ± 0.7 | .628 |
| MMP-9 | 22.2 ± 24.0 | .008b | 0.9 ± 0.5 | .366 |
| UBP43 | 9.3 ± 10.7 | .026a | 1.0 ± 0.1 | .497 |
| TIM1 | 5.1 ± 4.0 | .002b | 1.4 ± 1.7 | .815 |
| TIM3 | 3.1 ± 1.7 | .264 | 0.5 ± 0.2 | .060 |
| EMAP2 | 10.5 ± 16.4 | .175 | 2.6 ± 3.1 | .428 |
| GNLY | 15.3 ± 27.9 | .165 | 0.9 ± 0.1 | .191 |
| ICAM-1 | 17.7 ± 24.3 | .020a | 1.0 ± 0.1 | .842 |
| PD1 | 39.4 ± 47.3 | .025a | 1.7 ± 1.8 | .976 |
| SLPI | 45.2 ± 56.6 | .000b | 1.1 ± 0.0 | .105 |
| ECF-L | 3.0 ± 3.6 | .311 | UD | UD |
| EDN1 | 11.5 ± 11.4 | .031a | 1.0 ± 0.0 | .753 |
| FasL | 4.6 ± 6.4 | .483 | 0.5 ± 0.2 | .043 |
| ISG15 | 54.4 ± 31.8 | .019a | 1.0 ± 0.0 | .793 |
| MPIF1 | 1.3 ± 1.5 | .198 | 1.4 ± 2.1 | .411 |
| PDL1 | 15.4 ± 16.9 | .059 | UD | UD |
| PDL2 | 52.9 ± 39.0 | .031a | 2.0 ± 2.6 | .858 |
| PRF1 | 43.9 ± 62.8 | .000b | 2.7 ± 2.3 | .413 |
| STAT1 | 164.2 ± 133.7 | .000b | 1.0 ± 0.1 | .388 |
| STAT6 | 28.9 ± 48.0 | .141 | 1.0 ± 0.1 | .519 |
| TLR2 | 33.9 ± 29.2 | .008b | 1.0 ± 0.1 | .668 |
NOTE. Peripheral-blood lymphocytes (PBLs) were collected from 4 rhesus monkeys before (week 0) and after (week 5) BCG vaccination/infection and assessed for global gene expression by a large-scale real-time quantitation system. Earlier studies had shown peak T cell responses and anti-BCG immunity occurring 5 weeks after intravenous BCG inoculation [14–16]. BCG data show the means of fold changes in expression levels for week 5 vs. week 0 in PBLs from the 4 BCG-vaccinated monkeys. P values for IL-1, IL-2, IL-4, IL-5, IL-6, and IL-9 were >.05 at this 5-week time point but were <.05 in the longitudinal analysis (table 4). As validation, the control data show the means of fold changes in expression levels for week 2 vs. week 0 in PBLs from 4 normal, uninfected rhesus macaques that received saline. UD, undetectable.
a
P < .05.
b
P < .01.