Search results for "Complex."
showing 10 items of 5824 documents
LFA-1 Contributes to Signal I of T-Cell Activation and to the Production of Th1 Cytokines
2010
The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells. Compared with wild-type controls, CD18(-/-) T cells proliferated normally when stimulated with antibodies against CD3 and CD28, but secreted significantly less IFN-gamma and IL-2 than their wild-type counterparts. However, when T cells were stimulated with dendritic cells (DCs) that provide additional LFA-1 ligation, the pro…
Specific Targeting of Cytokine-Secreting Cells: A Bispecific Diabody Recognizing Human Interleukin-6 and CD3 Induces T Cell-Mediated Killing
1998
Cytokines have been implicated in the pathophysiology of many diseases. Although there have been many attempts to neutralize the activity of cytokines in vivo and in vitro, no strategies have been developed to specifically eliminate cells that overexpress cytokines. Considering the fact that cytokines in part remain cell associated on secretion, we have constructed a bispecific diabody consisting of a nonneutralizing scFv antibody recognizing human interleukin-6 (IL-6) and an scFv corresponding to the monoclonal antibody (mAb) OKT3, which recognizes and activates the human T cell receptor. Here we show that the diabody recognized both human IL-6 and human CD3. In the presence of human T cel…
Differential effects of IL-10 on proliferation and cytokine production of human gamma/delta and alpha/beta T cells.
1994
Gamma/delta TCR bearing T lymphocytes represent a T-cell subset whose functional relevance remains unclear. Nevertheless these T cells may play a role in the early immune response against bacteria. Until now the regulatory mechanisms on this response have not been investigated. The study described here evaluated the immunoregulatory effects of Interleukin-10 on gamma/delta and alpha/beta TCR-positive T-cell clones and freshly isolated peripheral-blood mononuclear cells (PBMC). IL-10 has been shown previously to inhibit lectin and antigen-induced proliferation and cytokine production by alpha/beta T cells. The results outlined below show that rhIL-10 strongly inhibits lectin-induced producti…
Catumaxomab: a bispecific trifunctional antibody.
2009
The trifunctional bispecific monoclonal antibody catumaxomab has two binding specificities directed at epithelial cell adhesion molecule (EpCAM) and the T-cell antigen CD3. With its Fc-fragment, catumaxomab additionally binds accessory cells such as dendritic cells, macrophages and natural killer cells. The trifunctional approach thus leads to unrestricted but specific killing of epithelial tumor cells by major histocompatibility complex without the need for preactivation or external costimulation. The tumor-associated antigen EpCAM is strongly expressed in carcinomas of various origins including colon, rectum, ovarian, gastric, esophagus, lung, pancreas, breast and head and neck. Expressio…
Tumor-specific T cell activation by recombinant immunoreceptors: CD3 zeta signaling and CD28 costimulation are simultaneously required for efficient …
2001
Abstract Recombinant immunoreceptors with specificity for the carcinoembryonic Ag (CEA) can redirect grafted T cells to a MHC/Ag-independent antitumor response. To analyze receptor-mediated cellular activation in the context of CD28 costimulation, we generated: 1) CEA+ colorectal tumor cells that express simultaneously B7-1 and B7-2, and 2) CEA-specific immunoreceptors that harbor intracellularly the signaling moities either of CD28 (BW431/26-scFv-Fc-CD28), CD3ζ (BW431/26-scFv-Fc-CD3ζ), or FcεRIγ (BW431/26-scFv-Fc-γ). By retroviral gene transfer, we grafted activated T cells from the peripheral blood with these immunoreceptors. T cells that express the FcεRIγ or CD3ζ signaling receptor lyse…
In vitro generation of CD4+CD25+ regulatory cells from murine naive T cells
2007
CD4+ CD25+ regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Recent data indicate that Tregs not only develop in the thymus during ontogeny but can also differentiate from naive T cells in the periphery. The following protocol describes a method by which Tregs are generated in vitro by stimulation of naive T cells in the presence of transforming growth factor beta (Ti-Tregs). In vitro-induced regulatory T cells express markers of conventional Treg such as CD25 and the genetic program committing transcription factor FoxP3. Functionally the in vitro-generated Ti-Tregs suppress T-cell activation and proliferation while in vivo these cells have been proven t…
Analysis of parathyroid graft rejection suggests alloantigen-specific production of nitric oxide by iNOS-positive intragraft macrophages
2009
Abstract Background During acute rejection of organ or tissue allografts T cells and macrophages are dominant infiltrating cells. CD4-positive T cells are important for the induction of allograft rejection and macrophages are important effector cells mediating cytotoxicity via production of nitric oxide (NO) by the inducible NO-synthase (iNOS). In the present study we analysed whether the destruction of primarily nonvascularised parathyroid allografts is also mediated by iNOS-positive macrophages. Methods Hypocalcaemic Lewis rats received parathyroid isografts (from Lewis donors) and allografts (from Wistar Furth donors), respectively, under the kidney capsule. Levels of serum calcium above…
MHC class II tetramer guided detection of Mycobacterium tuberculosis-specific CD4+ T cells in peripheral blood from patients with pulmonary tuberculo…
2007
Novel diagnostic tools are needed to diagnose latent infection and to provide biologically meaningful surrogate markers to define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have recently been developed in addition to the more than 100-year-old tuberculin skin test (TST) for the immune diagnosis of MTB in blood. The advent of soluble MHC/peptide tetramer molecules allows to objectively enumerate antigen-specific T cells. We identified novel MHC class II-restricted MTB epitopes and used HLA-DR4 tetrameric complexes to visualize ex vivo CD4(+) T cells directed against the antigens Ag85B and the 19-kDa lipoprotein, shared between MTB and ot…
Ci8 short, a novel LPS-induced peptide from the ascidian Ciona intestinalis,modulates responses of the human immune system
2017
The selective modulation of immunity is an emerging concept driven by the vast advances in our understanding of this crucial host defense system. Invertebrates have raised researchers’ interest as potential sources of new bioactive molecules owing to their antibacterial, anticancer and immunomodulatory activities. A LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates the transcript, Ci8 short, with cisregulatory elements in the 3′ UTR region that are essential for shaping innate immune responses. The derived amino acidic sequence in silico analysis showed specific binding to human Major Histocompatibility Complex (MHC) Class I and Class II alleles. The role of Ci…
Glycoprotein 96-activated dendritic cells induce a CD8-biased T cell response.
2005
Heat shock proteins (Hsps) are able to induce protective immune responses against pathogens and tumors after injection into immunocompetent hosts. The activation of components of the adaptive immune system, including cytotoxic T lymphocytes specific for pathogen- or tumor-derived peptides, is crucial for the establishment of immuno- protection. Hsps acquire these peptides during intracellular protein degradation and when released during necrotic cell death, facilitate their uptake and Minor Histocompatibility Complex (MHC)-restricted representation by professional antigen-presenting cells (APCs). In addition, the interaction of Hsps with APCs, including the Endoplasmatic Reticulum (ER)-resi…