A5029617753- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Cutaneous lymphoproliferative disorders research
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Inflammatory Myopathies and Dermatomyositis
- Lymphoma Diagnosis and Treatment
- Immune cells in cancer
- Toxoplasma gondii Research Studies
- Viral Infectious Diseases and Gene Expression in Insects
- T-cell and Retrovirus Studies
- Research on Leishmaniasis Studies
- Toxin Mechanisms and Immunotoxins
- Monoclonal and Polyclonal Antibodies Research
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- Cancer Research and Treatments
- Sarcoidosis and Beryllium Toxicity Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cannabis and Cannabinoid Research
- Venomous Animal Envenomation and Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- NF-κB Signaling Pathways
University of Pennsylvania
2005-2024
Philadelphia University
2008
The Wistar Institute
1994-2005
University of Veterinary Medicine
1998
Osaka University
1997
Johns Hopkins University
1996-1997
National Institute of Allergy and Infectious Diseases
1994-1996
Johns Hopkins Medicine
1996
University of Münster
1996
National Institutes of Health
1994
Abstract Dendritic cells are APCs that unique in their potency to stimulate proliferation of primary Ag-specific responses vitro and vivo. In this study, we demonstrate dendritic can produce IL-12, a dominant cytokine involved the development IFN-gamma-producing T cells. This finding resulted from our observations cell-induced Th1 total CD4+ upon neutralization endogenous levels IL-4 was IL-12-dependent. Furthermore, induce naive LECAM-1bright obtained alpha beta-TCR transgenic mice,...
To examine the function of IL-10 synthesis during early infection with intracellular protozoan Toxoplasma gondii, knockout (KO) mice were inoculated an avirulent parasite strain (ME-49). In contrast to control littermates that displayed 100% survival, IL-10-deficient animals succumbed within first 2 wk infection, no evidence enhanced proliferation. The mortality in KO was associated liver pathology characterized by increased cellular infiltration and intense necrosis. Levels IL-12 IFN-gamma...
In vitro and in vivo studies were performed to assess the involvement of IL-12 resistance acute chronic infection with an avirulent strain Toxoplasma gondii. Our previous findings implicated macrophages as a major source parasite-induced IL-12. This finding was confirmed by showing that peritoneal exposed either live parasites or soluble tachyzoite Ags produce protein. mice, increased expression (p40) mRNA both spleen cells detected early 2 days postinfection. Treatment neutralizing mAbs...
Protection induced by vaccination depends on the capacity of vaccine to elicit an appropriate immune response. In leishmaniasis, protection requires leishmanial-specific CD4 + T helper (T H ) cells. Vaccination BALB/c mice with leishmanial antigens and interleukin-12 (IL-12) promoted development 1 These were resistant subsequent infection Leishmania major . Thus, IL-12 is effective adjuvant for initiation protective cell-mediated immunity against leishmaniasis may be important component in...
The mechanisms of malignant cell transformation caused by the oncogenic, chimeric nucleophosmin (NPM)/anaplastic lymphoma kinase (ALK) remain only partially understood, with most previous studies focusing mainly on impact NPM/ALK survival and proliferation. Here we report that NPM/ALK-carrying T (ALK+TCL) cells strongly express immunosuppressive cell-surface protein CD274 (PD-L1, B7-H1), as determined mRNA level. expression is strictly dependent enzymatic activity NPM/ALK, demonstrated...
The mechanisms underlying the profound suppression of cell-mediated immunity (CMI) accompanying measles are unclear. Interleukin-12 (IL-12), derived principally from monocytes and macrophages, is critical for generation CMI. Measles virus (MV) infection primary human specifically down-regulated IL-12 production. Cross-linking CD46, a complement regulatory protein that cellular receptor MV, with antibody or activation product C3b similarly inhibited monocyte production, providing plausible...
Abstract Several cytokines, in particular tumor necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ), have been shown to be responsible for pathological reactions which may lead shock death observed infection with Gram‐negative bacteria response endotoxins (lipopolysaccharides, LPS). Priming of mice the avirulent Bacille Calmette Guérin (BCG) vaccine strain Mycobacterium bovis increases sensitivity lethal effect LPS results an efficient priming cytokine production. In low doses (1 γg/mouse)...
Infection of mice with the protozoan Leishmania major is an established in vivo model for definition factors that contribute to CD4+ T helper cell subset development. In current study, a central role IL-12 directing both innate and adaptive immune responses L. established. We show neutralization eliminates NK cytotoxic response IFN-gamma production by lymph node cells from 2-day major-infected C3H mice. Moreover, anti-IL-12 treatment abrogated Th1 development enhanced Th2 Consistent these...
The antitumor effect and mechanisms activated by murine IL-12 IL-18, cytokines that induce IFN-gamma production, were studied using engineered SCK mammary carcinoma cells. In syngeneic A/J mice, cells expressing mIL-12 or mIL-18 less tumorigenic formed tumors more slowly than control Neither SCK.12 nor SCK.18 protected significantly against tumorigenesis distant However, inoculation of the two cell types together synergistically 70% mice from concurrently injected 30% established 3 d...
We have previously shown that dendritic cells isolated after overnight culture, which can express B7 and are potent stimulators of naive T cell proliferation, relatively poor at inducing the proliferation a panel murine helper 1 (Th1) clones. Maximal stimulation Th1 clones was achieved using unseparated splenic antigen presenting (APC). An explanation for these findings is provided in present study where we show FcR+ L transfected with stimulate minimal response to anti-CD3 antibodies,...
Abstract Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by the expansion activated oligoclonal CD4+ T cells and macrophages at sites disease. To investigate immunopathogenesis sarcoidosis, we analyzed patterns cytokine expression in bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis idiopathic fibrosis normal volunteers. We found dominant type 1 expression, elevated mRNA protein levels IFN-gamma, but not IL-4, sarcoid lung compared...
Expression of a dominant negative mutant IFNgammaR1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFNgamma vitro more tumorigenic less responsive IL-12 therapy vivo. induced histologic evidence ischemic damage only IFNgamma-responsive tumors, vivo Matrigel vascularization assays revealed that while -unresponsive angiogenesis equally well, its downstream mediator inhibited by the cells. inhibitory activity cells, which may be attributable production chemokine...
The Shwartzman reaction is elicited by two injections of lipopolysaccharide (LPS) in mice. priming LPS injection given the footpad, whereas lethal challenge intravenously 24 h later. interferon gamma (IFN-gamma) or interleukin 12 (IL-12) instead induced mice further challenged with LPS. Antibodies against IFN-gamma when together agent, prevented primed either LPS, IL-12, IFN-gamma. IL-12 but not These results strongly suggest that induces release production IFN-gamma, and cytokine primes...
Abstract The immunomodulatory properties of thalidomide are currently being exploited therapeutically in conditions as diverse erythema nodosum leprosum, chronic graft-vs-host disease, rheumatoid arthritis, and sarcoidosis. relevant mechanism action these diseases remains unclear. important role recently ascribed to IL-12, a cytokine critical the development cellular immune responses, pathogenesis several led us examine whether affects production IL-12. Thalidomide potently suppressed IL-12...
Most patients treated with US Food and Drug Administration (FDA)–approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR have not been curative against solid cancers several hematological malignancies such as cell lymphomas, which very poor prognoses. One of the main barriers to clinical success adoptive immunotherapies is dysfunction lack expansion and/or persistence after infusion. In this study, we found that CD5 inhibits activation...
Abstract Interleukin‐12 (IL‐12, p70) a heterodimeric cytokine of p40 and p35 subunits, important for Th1‐type immune responses, has been attributed prominent role in multiple sclerosis (MS) its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the related cytokine, IL‐23, composed same subunit as IL‐12 unique p19 subunit, was shown to be involved Th1 responses EAE. We investigated whether astrocytes microglia, CNS cells with antigen‐presenting cell (APC) function can...
Endotoxin tolerance, the down-regulation of a subset endotoxin-driven responses after an initial exposure to endotoxin, may provide protection from uncontrolled immunological activation acute endotoxic shock. Recent data suggest, however, that inhibition monocyte/macrophage function associated with endotoxin tolerance can lead inability respond appropriately secondary infections in survivors IL-12 production by antigen-presenting cells is central orchestration both innate and acquired...
Abstract Endotoxin tolerance, the transient, secondary down-regulation of a subset endotoxin-driven responses after exposure to bacterial products, is thought be an adaptive response providing protection from pathological hyperactivation innate immune system during infection. However, although protecting development sepsis, endotoxin tolerance also can lead fatal blunting immunological subsequent infections in survivors septic shock. Despite considerable experimental effort aimed at...
Recombinant interleukin 12 (IL-12) can profoundly suppress cellular immune responses in mice. To define the underlying mechanism, recombinant murine (rm)IL-12 was given to C57BL/6 mice undergoing alloimmunization and found transiently but vivo vitro allogeneic splenocyte mitogenic responses. Use of neutralizing antibodies genetically deficient showed that IFN-γ (but not TNF-α) mediated rmIL-12–induced suppression. Splenocyte fractionation studies revealed adherent cells from rmIL-12–treated...
Abstract Retroviral‐mediated cytokine gene transfer into tumor cells is a highly effective way of inducing inhibition and immunity. We analyzed the tumorigenicity C‐26 murine colon carcinoma transduced with genes encoding two subunits interleukin‐12 (IL‐12) in polycistronic retroviral vector selected for resistance to G418 IL‐12 production (30–80 pg/ml). BALB/c mice injected s.c., i.v. intrasplenically C‐26/IL‐12 from three different IL‐12‐producing clones showed delayed onset as compared...
IL-12 is a heterodimeric cytokine with powerful positive regulatory influence on the development of Th1 cell-mediated immune responses. cells are critically involved in contact hypersensitivity (CHS), so we were interested studying whether relevance induction phase CHS. BALB/c mice sensitized by epicutaneous application 0.5% 2,4-dinitrofluorobenzene (DNFB) abdomen, draining lymph nodes obtained at various time points thereafter. RNA was extracted, and PCR analysis performed using primers...
Abstract In this study, we compared the effects of interleukin-2 (IL-2), IL-15, and IL-21 on gene expression, activation cell signaling pathways, functional properties cells derived from CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 IL-15 modulated, in a CTCL line, expression >1,000 transcripts by at least 2-fold, up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation Jak1 Jak3 lines native leukemic (Sezary) cells. However, only strongly...