Respiratory infections are the third leading cause of death worldwide. Illness is caused by pathogen replication and disruption of airway homeostasis by excessive expansion of cell numbers. One strategy to prevent lung immune-mediated damage involves reducing the cellular burden. To date, antiinflammatory strategies have affected both antigen-specific and naive immune repertoires. Here we repor...

Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 cost...

Systemic lupus erythematosus (SLE) is a devastating systemic inflammatory disease, with prominent female bias. Recent literature suggests the OX40/OX40L costimulatory pathway may play an important role in development of SLE. GWAS have identified TNFSF4 (OX40L) as SLE susceptibility locus. OX40L stimulation T cells through OX40 receptor has been shown to promote follicular helper (Tfh) phenotype...

Adoptive therapy of cancer with genetically redirected T cells showed spectacular efficacy in recent trials. A body of pre-clinical and clinical data indicate that young effector and central memory T cells perform superior in a primary anti-tumor response; repetitive antigen engagement, however, drives T cell maturation to terminally differentiated cells associated with the loss of CCR7 which e...

Fresh leukemic cells from patients with adult T cell leukemia (ATL) and some ATL-derived T cell lines show adhesion to human umbilical vein endothelial cells (HUVECs) mainly through E-selectin, but a proportion of this binding remains unaffected by the addition of combinations of antibodies against known adhesion molecules. By immunizing mice with one of such cell lines, we established monoclon...

Targeted immunotherapy, such as anti-CTLA-4 and anti-PD-1, has proven effective in treating cancer patients. However, despite these advances, cancer remains the second leading cause of death in the US. More effective strategies designed to maximize antitumor CD8 T cell responses are necessary to sustain long-term immunity. Agonist anti-OX40 and antagonist anti-CTLA-4 mAb augment the CD8 T cell ...

This report investigates the role of OX40 ligand (OX40L) and its receptor, OX40, expressed on activated B and T cells, respectively, in promoting the differentiation of T helper type 2 (Th2) CD4 T cells. These molecules are expressed in vivo by day 2 after priming with T cell– dependent antigens. Their expression coincides with the appearance of immunoglobulin (Ig)G switch transcripts and mRNA ...

Ligation of the TNF receptor family costimulatory molecule OX40 (CD134) with an agonist anti-OX40 monoclonal antibody (mAb) enhances antitumor immunity by augmenting T-cell differentiation as well as turning off the suppressive activity of the FoxP3(+)CD4(+) regulatory T cells (Treg). In addition, antibody-mediated blockade of the checkpoint inhibitor CTLA-4 releases the "brakes" on T cells to ...

NF-κB signalling plays an essential role in T cell activation and generation of regulatory and memory populations in vivo. In the present study, we aimed to investigate the role of NF-κB signalling in post-activation T cells using tissue specific ablation of inhibitor of kappa-B kinase 2 expression, an important component of the inhibitor of kappa-B kinase complex in canonical NF-κB signalling....

OX40 is a costimulatory molecule that belongs to the tumor necrosis factor receptor (TNFR) superfamily. agonist-based combinations are emerging as promising candidates for novel cancer immunotherapy. Clinical trials have shown agonist antibodies could lead better results in patients. Using hybridoma platform and three different types of immunization strategies, namely recombinant protein, DNA, ...