Table 2.
Summary of EMMPRIN studies and relevance to T cells
| Relevance | Manipulation | Observation |
|---|---|---|
| Thymus Positive/facilitatory role for EMMPRIN High EMMPRIN levels | ||
| T cell development | EMMPRIN mAb (RL73.2) on thymocytes [45] | Decreased DN4, DP, CD4+ SP populations |
| Lck‐cre; EMMPRIN flox/flox thymocytes [46] | Decreased DP, CD4+ SP populations (DN4 not assessed) | |
| Periphery Negative/inhibitory role for EMMPRIN Low EMMPRIN levels | ||
| T cell activation | TCR‐mediated activation of human T cells [51, 52] | Identified EMMPRIN at immune synapses |
| EMMPRIN mAb (MEM‐M6/6, 5A12) on human T cells upon TCR‐mediated activation [51, 52] | Altered immune synapse formation | |
| CD48 and CD59 displaced from lipid rafts | ||
| Decreased CD25, tyrosine phosphorylation, cytokines | ||
| Proliferation | EMMPRIN−/− splenocytes in a MLR [30] | Increased proliferation |
| Lck‐cre; EMMPRIN flox/flox T cells upon anti‐CD3/CD28 stimulation [46] | Increased proliferation | |
| EMMPRIN siRNA KD in human T cells and PHA activation [50] | Increased proliferation | |
| EMMPRIN mAb (MEM‐M6/6, 5A12, clone 10, M6‐1B9, UM‐8D6, HI197) on human PBMCs and/or purified T cells upon TCR‐mediated activation [48, 51, 52, 53–54, 58] | Decreased proliferation | |
| Periphery Positive/facilitatory role for EMMPRIN High EMMPRIN levels | ||
| Migration | EMMPRIN mAb (UM‐8D6) on human T cells [49] | Decreased CyPA‐mediated migration |
| EMMPRIN mAb (RL73.2) in the mouse system [61, 62–63] | Decreased CyPA‐mediated migration | |
| EMMPRIN KD or EMMPRIN mAb (HAb18) in/on Jurkat cells [59, 77] | Decreased transendothelial migration and CyPA‐mediated migration | |
| Invasion | EMMPRIN mAb (UM‐8D6, clone 10) in cocultures of mouse mϕ or fibroblasts with human T cells [53, 61] | Inhibited MMP‐9 secretion |
| EMMPRIN activity‐blocking peptide in cocultures of transformed human T cells and fibroblasts [75] | Decreased MMP‐2 stimulation | |
| Adhesion | Immunoprecipitation and co‐localization experiments in cell lines [78] | Identified EMMPRIN to interact with β1 integrins |
| EMMPRIN mAb (HIM6) on human PBMCs and THP‐1 cells [24, 79, 81] | Reduced CyPB‐induced P‐ERK and adhesion to fibronectin | |
| Identified EMMPRIN‐CyPB‐CD98‐β1 integrin complexes | ||
| EMMPRIN mAb (clone 10) upon TCR‐mediated activation of human PBMCs [66] | Decreased α4 integrin levels | |
| Decreased adhesion to endothelial cells | ||
| EMMPRIN mAb (MEM‐M6/8, HAb18) on Jurkat cells [23, 59] | Induced homotypic cell aggregation and adhesion to a LFA‐1 ligand | |
| Identified CD43‐EMMPRIN complexes | ||
| EMMPRIN KD in Jurkat cells [59, 77] | Reduced adhesion to ECM fibronectin | |
| Induced homotypic cell aggregation, decreased CD98 expression | ||
| Energy metabolism | EMMPRIN siRNA KD in human cell lines [25, 82, 83, 89] | Decreased MCT1/4 expression and efflux of toxic lactic acid byproducts |
| Identified MCT‐EMMPRIN complexes | ||
| MCT1 inhibition in human PBMCs [90] | Decreased T cell proliferation and lactate efflux | |
| Proliferation | EMMPRIN siRNA KD in Jurkat cells or other cell lines [77, 89] | Decreased proliferation |
A positive/facilitatory role for EMMPRIN exists when EMMPRIN expression levels are high and a negative/inhibitory role when EMMPRIN expression levels are low. KD, Knockdown; mϕ, macrophages; P‐ERK, phosphorylated ERK.