Cognate interactions between T follicular helper (Tfh) cells and B are essential for promoting protective Ab responses. Whereas costimulatory receptors such as ICOS accepted being important the induction of Tfh cell fate decision, other molecules may play key roles in amplifying or maintaining phenotype. In this study, with vaccinia virus infection mice, we show that OX40 was expressed on accumulated at T/B borders white pulp spleen OX40-dependent signals directly shaped magnitude quality...

In establishing a respiratory infection, vaccinia virus (VACV) initially replicates in airway epithelial cells before spreading to secondary sites of mainly the draining lymph nodes, spleen, gastrointestinal tract, and reproductive organs. We recently reported that interferon gamma (IFN-γ) produced by CD8 T ultimately controls this disseminated but relative contribution IFN-γ early infection is unknown. Investigating role innate immune cells, we found frequency natural killer (NK) lung...

The precise immune components required for protection against a respiratory Orthopoxvirus infection, such as human smallpox or monkeypox, remain to be fully identified. In this study, we used the virulent Western Reserve strain of vaccinia virus (VACV-WR) model primary infection. Naive mice infected with VACV-WR mounted an early CD8 T cell response directed dominant and subdominant Ags, followed by CD4 Ig response. contrast other infection models that highlight critical requirement cells Ig,...

CD8 T cells are a key component of immunity to many viral infections. They achieve this through using an array effector mechanisms, but precisely which component/s required for protection against respiratory orthopox virus infection remains unclear. Using model vaccinia in mice, we could specifically determine the relative contribution perforin, TRAIL, and IFN-γ-mediated pathways induced morbidity mortality. Unexpectedly, observed that death was mediated by IFN-γ without any involvement...

Abstract Phenotypically diverse memory CD 8 + T cells are present in the lungs that either re‐circulate or reside within tissue. Understanding key cellular interactions regulate generation and then persistence of these different subsets is great interest. Recently, DNGR ‐1 dendritic cell ( DC ) mediated priming was reported to control lung‐resident but not circulating following respiratory viral infection. Here, we report an important role for Ly6C inflammatory monocytes IM s) contributing...

During respiratory infection with vaccinia virus (VacV), a member of Poxviridae family, CD8 + T cells play important role in resolving the primary infection. Effector clear by accumulating infected lungs large numbers and secreting molecules such as IFN-γ that kill virally cells. However, precise cell types regulate generation effector are not well defined. Dendritic (DCs) heterogeneous population immune recognized key initiators regulators T-cell-mediated immunity. In this study, we reveal...

Abstract The transition of effector T cells or memory precursors into distinct long-lived cell subsets is not well understood. Although many molecules made by APCs can contribute to clonal expansion and differentiation, it clear if contraction development passive active. Using respiratory virus infection, we found that CD8 cannot express the TNF family molecule lymphotoxin-like, exhibits inducible expression, competes with HSV glycoprotein D for herpes entry mediator, a receptor expressed...

How tissue-specific anatomical distribution and phenotypic specialization are linked to protective efficacy of memory T cells against reinfection is unclear. Here, we show that lung environmental cues program recently recruited central-like with migratory potentials for their functions during lethal respiratory virus infection. After entering the lung, some retain original CD27hiCXCR3hi phenotype, enabling them localize near infected bronchiolar epithelium airway lumen function as first line...

CD8+ T cells play an important role in host resistance to many viral infections, but the underlying transcriptional mechanisms governing their differentiation and functionality remain poorly defined. By using a highly virulent systemic respiratory poxvirus infection mice, we show that transcription factor Bcl11b provides dual trigger sustains clonal expansion of virus-specific effector cells, while simultaneously suppressing expression surface markers associated with short-lived cell (SLEC)...

Attenuated vaccinia virus (VACV) vectors are considered prime vaccine candidates for use in immunotherapy of infectious disease. In spite this, recent data show that the level attenuation may hamper efficient generation protective CD8 T cells. This suggests additional adjuvant-like activities need to be combined with attenuated VACV optimal vaccination. Stimulatory reagents TNFR family molecule 4-1BB (CD137) represent such an adjuvant Previous murine studies have found can participate...

ABSTRACT Antibody production by B cells in the absence of CD4 T cell help has been shown to be necessary and sufficient for protection against secondary orthopoxvirus (OPV) infections. This conclusion is based on short-term depletion leukocyte subsets vaccinated animals, addition passive transfer immune serum naive hosts that are subsequently protected from lethal infection. Here, we show neutralizing antibody virus control during a ectromelia (ECTV) A crucial role was revealed when this...

ABSTRACT A pivotal role for antigen-specific recall responses to secondary virus infection is well established, but the contribution of innate immune cells this process unknown. Recovery mice from a primary orthopoxvirus (ectromelia [ECTV]) requires function natural killer (NK) cells, granulocytes, plasmacytoid dendritic (pDC), T and B cells. However, during challenge, resolution thought be dependent on antibody not cell function. We investigated NK pDC control challenge in that had been...

Following a respiratory virus infection, CXCR3hi CX3CR1lo and CXCR3lo CX3CR1hi CD8 T cells localize to different compartments within the lung play an important role in host resistance, but mechanisms governing their optimal generation are poorly defined. We serendipitously found that B cell-deficient (μMT-/-) mice were highly resistant lethal infection with virulent poxvirus strain depletion of rendered these susceptible infection. not required for expansion virus-specific cells, greater...

Abstract CD8 memory T cells play a critical role in protection against repeated exposure to respiratory viruses. Memory cell development the lung is still not fully understood terms of nature and source molecular signals that establish maintain state. LIGHT tumor necrosis factor family member expressed by immune such as activated cells, dendritic monocytes granulocytes. It known interact with two receptors HVEM & LTβR, leading differential outcomes. However, specifically during viral...

e14016 Background: We are focused on developing and optimizing a next generation cellular vaccine platform – referred to as ComPACT (COMbination Pan-Antigen Cytotoxic Therapy), that incorporates tumor antigen chaperone (gp96-Ig) with T-cell costimulation (OX40L-Ig), into single cell line overexpressing host of cancer associated neoantigens. Viagenpumatucel-L (HS-110; ImPACT), human lung adenocarcinoma line, stably transfected express gp96-Ig, is being tested in phase 1/2 clinical trial...

Abstract Our technology is focused on developing a next generation cellular vaccine platform – referred to as ComPACT (COMbination Pan-Antigen Cytotoxic Therapy), that incorporates tumor antigen chaperone (gp96-Ig) with T-cell costimulation (OX40L-Ig), into single cell line secretes both. Viagenpumatucel-L (HS-110; ImPACT), human lung adenocarcinoma line, stably transfected express gp96-Ig being tested in phase 1/2 clinical trial (NCT#02439450) checkpoint inhibition for NSCLC. A similar...

Our technology is focused on developing a next generation cellular vaccine platform – referred to as ComPACT (COMbination Pan-Antigen Cytotoxic Therapy), that incorporates tumor antigen chaperone (gp96-Ig) with T-cell costimulation (OX40L-Ig), into single cell line secretes both. Viagenpumatucel-L (HS-110; ImPACT), human lung adenocarcinoma line, stably transfected express gp96-Ig being tested in phase 1/2 clinical trial (NCT#02439450) checkpoint inhibition for NSCLC. A similar generated...

Abstract We have developed a next generation cellular vaccine platform that incorporates tumor antigen chaperone (gp96-Ig) in cell line and host of over-expressed cancer associated neoantigens. Viagenpumatucel-L (HS-110), human lung adenocarcinoma line, stably transfected to express gp96-Ig, is being tested phase 1/2 clinical trial (NCT#02439450) for NSCLC. Heat has recently HS-130, an allogeneic cell-based vaccine, designed secrete tumor-associated antigens along with costimulatory...

Abstract TNFRSF25, also known as Death Receptor 3 (DR3), is a cell surface receptor of the tumor necrosis factor superfamily (TNFRSF) which expressed on T cells, innate lymphoid and B cells. Upon binding with TL1A ligand, this co-stimulatory molecule induces activation, leading either to inflammation or death. Mouse PTX-35 (mPTX-35) TNFRSF25 functional agonist derived from CDR that was humanized affinity matured, then fused mouse IgG1-Fc backbone. Since costimulatory antibodies have shown...

Abstract Tumor cells evolve multiple mechanisms to escape immune surveillance, one of which is establish a tolerogenic microenvironment by recruiting suppressive cell types such as regulatory T (Tregs). Necrosis Factor Receptor Super Family 25 (TNFRSF25), also known Death 3 (DR3), potent costimulatory molecule and preferentially expressed activated antigen-experienced cells. PTX-35, potential first-in-class TNFRSF25 agonist antibody, currently in Phase 1 clinical trial patients with solid...