Patients suffering from cardiovascular disease have well-established atherosclerotic lesions, rendering lesion regression of therapeutic interest. The OX40 (TNFRSF4)-OX40 ligand (OX40L; TNFSF4) pathway is important for the proliferation and survival of T cells, stimulates B cells, and is associated with cardiovascular disease. We hypothesized that interference with the OX40-OX40L pathway, in co...

The TNF receptor-associated factor (TRAF) family of molecules acts as adapter proteins for signaling pathways initiated by several members of the TNF receptor (TNFR) superfamily. TRAF5(-/-) animals are viable and have normal development of the immune system despite interacting with several TNFR family members. A clear role for TRAF5 has yet to emerge. OX40 (CD134) interacts with TRAF5, suggesti...

Members of the TNF receptor (TNFR) superfamily are cell-surface proteins that can be found on most cell types including lymphocytes. Although some TNFR-related molecules are constitutively expressed, others, such as CD30 and Ox40, are induced upon activation of lymphocytes. CD30 and Ox40 are predominantly expressed on activated T helper (T(h))2 cells. Both receptors can activate c-Jun N-termina...

Background: OX40 (CD134) is a costimulatory molecule induced by its ligand (OX40L). expresses predominantly on activated/memory CD4+ T cells and regulatory (Treg) cells. Atopic dermatitis (AD) common inflammatory skin disease, currently considered as biphasic disease with TH2 predominating in the acute phase switching to TH1 skewing chronic phase. A recent clinical trial suggests monoclonal ant...

The authors regret that two of the fl ow cytometry histograms in Fig. 3 C were inadvertently duplicated. The corrected fi gure and its legend appear below. Figure 3. Tumor-infi ltrating T reg cells express functional OX40. (A) TILs were purifi ed from a pool of CT26 tumor nodules, and the CD4 + cell population was analyzed by fl ow cytometry (percentages are shown). As controls, CD4 + T cells w...

The central role of T cells in antitumor immunity is well established. However, tumor progression, often seen in the presence of substantial lymphocytic infiltration, suggests that these T cells are not capable of mounting an effective immune response to control tumor growth. Evidence has accumulated that T lymphocytes infiltrating human neoplasms are functionally defective, incompletely activa...

RATIONALE Patients with acute coronary syndrome (ACS) predisposed to recurrent coronary events have an expansion of a distinctive T-cell subset, the CD4(+)CD28(null) T cells. These cells are highly inflammatory and cytotoxic in spite of lacking the costimulatory receptor CD28, which is crucial for optimal T cell function. The mechanisms that govern CD4(+)CD28(null) T cell function are unknown. ...

Background Adoptive cell transfer (ACT) using tumor-infiltrating lymphocytes (TIL) has achieved an overall response rate of 39% in metastatic melanoma patients at Moffitt Cancer Center. In these trials, a substantial fraction were non-responders by RECIST, but demonstrated mixed to therapy. These results suggest that the infused TIL product contained tumor-reactive T cells with therapeutic pote...

Mice deficient in OX40 or 4-1BB costimulatory pathways show defects in T cell recall responses, with predominant effects on CD4 vs CD8 T cells, respectively. However, OX40L can also stimulate CD8 T cells and 4-1BBL can influence CD4 T cells, raising the possibility of redundancy between the two TNFR family costimulators. To test this possibility, we generated mice deficient in both 4-1BBL and O...