Independent studies have shown that CD27, 4-1BB, and OX40 can all promote survival of activated CD8+ T cells. We have therefore compared their impact on CD8+ memory T cell formation and responsiveness within one, physiologically relevant model system. Recombinant mice, selectively lacking input of one or two receptors, were challenged intranasally with influenza virus, and the immunodominant vi...

Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte-associated molecule 4-immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression in vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 T cells, a chemokine receptor linked wit...

Previously, the field of tumor immunology has relied on T cell receptor (TCR) transgenic mice and model tumor antigens to study the T cell:tumor cell interaction. However, these models have limitations. Namely, they do not reflect the natural affinity, repertoire, or precursor frequency of tumor antigen-specific T cells. Using a novel TCR affinity tool, the Nur77GFP mouse, we have characterized...

Adoptive therapy with chimeric antigen receptor (CAR) redirected T cells recently showed remarkable anti-tumor efficacy in early phase clinical trials; self-repression of the immune response by T-cell secreted cytokines, however, is still an issue raising interest to abrogate the secretion of repressive cytokines while preserving the panel of CAR induced pro-inflammatory cytokines. We here reve...

Recent clinical trials targeting the OX40-OX40L axis in atopic dermatitis/AD (AMG451, KHK4083, and KY1005) suggest potential for long-term disease modification. While inflammatory models that upregulate effector T cell survival inhibit Foxp3+ Tregs, mechanism of action remains unelucidated. We assessed OX40 OX40L expressing cells skin blood AD patients, identifying how they regulate effectors T...

PURPOSE To investigate the roles of interaction between OX40 and OX40 ligand (OX40L) in the development of experimental allergic conjunctivitis (EC) in mice. METHODS BALB/c mice actively immunized with short ragweed pollen (RW) were intraperitoneally injected on days 0, 2, 4, 6, and 8 with agonistic anti-OX40 Ab, blocking anti-OX40L Ab, or normal rat (nr)IgG. On day 10, the mice were challeng...

High glucose transporter 1 (Glut1) surface expression is associated with increased glycolytic activity in activated CD4+ T cells. Phosphatidylinositide 3-kinases (PI3K) activation measured by p-Akt and OX40 is elevated in CD4+Glut1+ T cells from HIV+ subjects. TCR engagement of CD4+Glut1+ T cells from HIV+ subjects demonstrates hyperresponsive PI3K-mammalian target of rapamycin signaling. High ...

Background: OX40 is a crucial T-cell costimulatory molecule, but its molecular characteristics remain unclear in diffuse large B-cell lymphoma (DLBCL). Methods: We performed an integrative analysis of gene expression, somatic mutations and multiplex immunofluorescence to characterize the features, tumor immune microenvironment (TiME) clinical outcomes. Results: first identified that abnormally ...

In this study we examined the role and regulation of OX40 signals during CD4 T cell priming on dendritic cells (DCs). Contrary to expectation, OX40-deficient cells proliferated more rapidly than their normal counterparts, particularly when stimulated with peptide in the absence of added cytokines. This proliferative advantage was not apparent for Th2-differentiated cells. When the reasons for t...

Our previous studies have implicated signaling through the tumor necrosis family receptors OX40 and CD30 as critical for maintaining CD4 memory responses. We show that signals through both molecules are also required for CD4 effector-mediated autoimmune tissue damage. Under normal circumstances, male mice deficient in the forkhead transcription factor FoxP3, which lack regulatory CD4 T cells, d...