Table I. Differential regulation of gene expression by IL-12 and IFNα.
Oligonucleotide microarray analysis was used to determine mRNA expression levels for naïve CD8 T cells stimulated with Ag and B7-1 in the absence or presence of IL-12 or IFNα. Expression of about 350 genes is regulated in common by the two cytokines, and each cytokine also uniquely regulates 200 to 300 genes, as illustrated here. Values shown for selected genes are the fold change at 72hr in mRNA expression level in the presence of the indicated cytokine in comparison to the level without cytokine added. Increases in expression are shown in red, decreases in green, and nc indicates no change in comparison to cells stimulated with just Ag and B7-1. Data are from Agarwal et.al. [28].
| Adhesion & Migration Differences | ||||
|---|---|---|---|---|
| IL-12 | IFNα | |||
| 72h | 72h | |||
| Fold Change Relative to | Function | |||
| Gene | 2 signal stimulation | |||
| Common to Both | ||||
| Xcl1 | 1.7 | 2.1 | CD4, DC recruit | chemokine (C motif) ligand 1 |
| Cxcr3 | −3.5 | −2.1 | intigrin activation, chemotactic migration | chemokine (C-X-C motif) receptor 3 |
| Itgb7 | −1.7 | −2.3 | mucosal migration | integrin beta 7 |
| Sell | −3.0 | −2.3 | L-selectin | selectin, lymphocyte |
| Ccr5 | 10.6 | 2.0 | migration to inflamm | chemokine (C-C motif) receptor 5 |
| Nptn | −1.9 | −1.7 | cell-cell, cell-substrate interactions | neuroplastin |
| IL-12 Only | ||||
| Ccl3 | 2.5 | nc | MIP-1a granulocyte activation, inflam cytokine | chemokine (C-C motif) ligand 3 |
| Ccl4 | 2.8 | nc | MIP-1b granulocyte activation, inflam cytokine | chemokine (C-C motif) ligand 4 |
| Ccr2 | 12.1 | nc | migration to inflamm | chemokine (C-C motif) receptor 2 |
| Cxcr4 | 1.7 | nc | chemotactic receptor (ligand is SDF-1 (CXCL12) | chemokine (C-X-C motif) receptor 4 |
| Cmtm7 | −2.0 | nc | chemokine-like super family | CKLF-like MARVEL |
| Itga4 | −2.0 | nc | alpha 4 integrin (with b1) homing receptor | integrin alpha 4 |
| Itga6 | −2.3 | nc | alpha 6 integrin | integrin alpha 6 |
| Lgals3 | 3.0 | nc | galectin-3 adhesion | lectin, galactose binding, soluble 3 |
| Nrp1 | −2.1 | nc | coreceptor of VEGF receptor, migration | neuropilin 1 |
| IFNa only | ||||
| Cd83 | nc | 2.6 | unknown function (on DC) | CD83 antigen |
| Cd83 | nc | 3.5 | unknown function (on DC) | CD83 antigen |
| Cxcl10 | nc | 2.8 | NK, B, neutrophil, TH1 attractant | chemokine (C-X-C motif) ligand 10 |
| Crtam | nc | −4.3 | on activated T’s, adhesion?? | cytotoxic and regulatory T cell molecule |
| Opposite | ||||
| Lgals9 | −2.0 | 1.9 | eosinophil attractant, galectin-9 | lectin, galactose binding, soluble 9 |