Table 1.
Summary of immune checkpoints cellular distribution and function.
| Immune Checkpoint Receptor | Cells Expressing Receptor | Ligand | Cells Expressing Ligand | Signaling Outcome in Sepsis |
|---|---|---|---|---|
| PD-1 (CD279) | - T cells - B cells - Monocytes - NK cells - Dendritic cells (21) |
PD-L1 | - T cells - B cells - Dendritic cells - Macrophages - Tumor cells - Lung, liver, heart, placenta, kidney and pancreas and other parenchymal cells (21, 22) |
- T cell exhaustion - Decreases myeloid cell function - Intestinal injury - Lung injury (18, 23–29) |
| PD-L2 | - Dendritic cells - Monocytes - Lung, liver, colon, small intestine, and placenta parenchymal cells (22, 30) |
- Deletion of PD-L2 improves bacterial clearance, with no observed survival benefit (30) |
||
| 2B4 (CD244) | - NK cells - T cells (31) |
CD48 | - All hematopoietic cells in humans (32) |
- T cell apoptosis - Increases PD-1 expression (33–35). |
| CTLA-4 (CD152) | - Activated CD4 and CD8 T cells | - CD80 - CD86 |
- Antigen presenting cells (36) |
- T cell apoptosis - Increased mortality (37, 38) |
| HVEM (CD270, TNFRSF14) | - Monocytes - Dendritic cells - Neutrophils - NK cells - Resting T cells - Immature B cells (39, 40) |
-BTLA (CD272) | - T cells - Monocytes - Macrophages - Dendritic cells (39–42) |
- Promotes CD4 T cell death - Inhibits innate leukocyte activation - Reduces bacterial clearance - Promotes organ injury (43) |
| LAG-3 (CD223) | - CD4, CD8, and regulatory T cells - B cells - Dendritic cells |
MHC II | - Antigen presenting cells | - Inhibits T cell responses - Decreases bacterial clearance (44) |
| TIM-3 | - NK cells - Macrophages - Dendritic cells - Mast cells - CD4 and CD8 T cells |
CEACAM1 | - Microvascular endothelia - Epithelial cells - T cells - B cells - Macrophages - Dendritic cells - Tumor cells (45) |
- Decreases inflammation - Decreases T cell apoptosis (46, 47) |
| Galectin 9 | - APCs, T cells, B cells -Liver - Small intestine - Thymus - Kidney - Spleen - Lung - Cardiac and skeletal muscle (48, 49) |
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| Ox40 (CD134) | - Activated CD4, CD8, and regulatory T cells - Activated NK cells (50–52) |
Ox40L (CD134L, CD252, glycoprotein 34) | - Macrophages - Dendritic cells - Langerhans cells - Vascular endothelial cells - Bronchial smooth muscle cells - Mast cells - Activated NK cells (53–60) |
- Improves outcomes in murine sepsis (61) |