Table 3.
Therapeutic effect of OX40–OX40L in autoimmunity disease.
| Autoimmunity | Model | Intervention and effect | Ref. |
|---|---|---|---|
| Experimental autoimmune encephalomyelitis (EAE) | Activated induced EAE murine model | A neutralizing OX40L mAb (RM134L) reduced mononuclear cell infiltration into the spinal cord | 80 |
| Adoptive transfer EAE murine model | OX40 immunotoxin injection resulted in amelioration of EAE | 81 | |
| EAE murine model | Soluble OX-40R treatment ameliorated both actively induced and adoptively transferred EAE disease | 82 | |
| OX40L-deficient mice (OX40L−/−) | Abortive T cell priming greatly reduced EAE clinical manifestations | 60 | |
| OX40L transgenic mice (OX40L-Tg) | OX40L-Tg mice developed a greater severity of EAE despite a delayed onset | 60 | |
| EAE Lewis rats | OX40 antibody enhances the autoantigen specific Vβ8.2+ T cells | 83 | |
| Systemic lupus erythematosus (SLE) | SLE patients | An increased frequency of peripheral CD4+OX40+ T cells in SLE patients | 84 |
| SLE patients | OX40L–OX40 axis contributes to the aberrant Tfh cell response | 33 | |
| SLE patients | The serum level of OX40L or OX40 expression on CD4+ T cells may act as markers of SLE | 85 | |
| SLE patients | Renal biopsies of SLE patients showed infiltration of OX40+ T cells | 86 | |
| SLE patients | OX40 mAb could inhibit expression of perforin and hemolysis activities to ameliorate SLE | 87 | |
| SLE patients | Whole genome association (WGA) studies of OX40L | 88 | |
| Rheumatoid arthritis (RA) | Collagen-induced arthritis (CIA) murine model | OX40 blockade reduced the proinflammatory responses and ameliorated RA development | 55 |
| CIA murine model | Anti-OX40L mAb ameliorated RA disease and suppressed IFN-γ and anti-CII IgG2a production | 61 | |
| CIA murine model and HTLV-I Tg mouse model. | Low OX40 expression on T cells inIL-1-deficient mice resulted in impaired suppression of RA | 89 | |
| RA patients | OX40 plasma levels were higher than control group treatment of methotrexate and adalimumab | 90 | |
| CIA murine model | Antigen inhibition of CIA is associated with induction of OX40 on T cells | 91 | |
| IL-1R deficient (IL-1Ra−/−) mice | Anti-OX40 Ab accelerated the production of IL-17 | 69 | |
| Colitis | Dextran sulfate sodium induced murine model | OX40-IgG treatment resulted in a dose-dependent reduction of intestinal inflammation | 92 |
| T cell transfer model of colitis | OX40 regulated the homeostasis of intestinal FOXP3+ Treg cells and suppressed colitis | 45 | |
| Crohn's disease murine model | Combination of anti-TNF-α and anti-OX40L mAbs improved the therapeutic effect of chronic colitis | 93 | |
| Biopsy specimens of patients | Positive of OX40 staining in all biopsies of patients with ulcerative colitis | 94 | |
| T cell-restored SCID mice | Anti-OX40L mAb completely blocked development of colitis | 62 | |
| Autoimmune experimental uveitis (AEU) | Ovalbumin-induced AEU | Anti-OX40L antibody substantially inhibited the antigen-specificocular inflammation | 31 |
| IRBP161-180 induced AEU | OX40-activating Ab prolonged and exacerbated the disease course of EAU | 95 | |
| Type 1 diabetes mellitus | Type 1 diabetes patients | Co-expression of CD25 and OX40 receptors delineates autoreactive T-cells in type 1 diabetes | 96 |
| Non-obese diabetic (NOD) mice | Inhibiting OX40–OX40L interactions at a late stage prevented diabetes development | 97 | |
| NOD mice | An OX40 agonistic antibody (OX86) treatment reduced type 1 diabetes (T1D) incidence | 98 | |
| Multiple sclerosis (MS) | Systemic sclerosis (SSc) patients | Serum soluble OX40 levels correlate with the early-onset of SSc disease | 99 |
| MS patients | CD4+ OX40+ T cells were not increased in clinically active MS | 100 | |
| MS patients | OX40 is upregulated in the CNS of MS patients | 101 | |
| MS patients | TNFSF4 polymorphisms can affect systemic sclerosis genetic susceptibility | 102 | |
| SSc patients | Polymorphisms in the TNFSF4 gene region are associated with susceptibility to SSc | 103 |