Search results for "G cell"
showing 10 items of 456 documents
Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review
2019
Background Vaccine adjuvants are compounds that significantly enhance/prolong the immune response to a co-administered antigen. The limitations of the use of aluminium salts that are unable to elicite cell responses against intracellular pathogens such as those causing malaria, tuberculosis, or AIDS, have driven the development of new alternative adjuvants such as QS-21, a triterpene saponin purified from Quillaja saponaria. Purpose The aim of this review is to attempt to clarify the mechanism of action of QS-21 through either receptors or signaling pathways in vitro and in vivo with special emphasis on the co-administration with other immunostimulants in new adjuvant formulations, called a…
Drug-induced expansion and differentiation of Vγ9Vδ2 T cells in vivo: The role of exogenous IL-2
2005
Human Vgamma9Vdelta2 T cells recognize nonpeptidic Ags generated by the 1-deoxy-d-xylulose 5-phosphate (many eubacteria, algae, plants, and Apicomplexa) and mevalonate (eukaryotes, archaebacteria, and certain eubacteria) pathways of isoprenoid synthesis. The potent Vgamma9Vdelta2 T cell reactivity 1) against certain cancer cells or 2) induced by infectious agents indicates that therapeutic augmentations of Vgamma9Vdelta2 T cell activities may be clinically beneficial. The functional characteristics of Vgamma9Vdelta2 T cells from Macaca fascicularis (cynomolgus monkey) are very similar to those from Homo sapiens. We have found that the i.v. administration of nitrogen-containing bisphosphonat…
Human GITR Ligand Is Expressed on Tumor Cells and Reduces Cytokine Production and Cellular Cytotoxicity of NK Cells Identified to Express GITR.
2005
Abstract Members of the tumor necrosis factor (TNF) superfamily mediate multiple cellular functions including cellular proliferation, differentiation, and cell death. Human Glucocorticoid-induced TNF Receptor (GITR) has been shown to be expressed on T cells, is upregulated following activation and mediates costimulatory signals. The human GITR ligand (GITRL) has been reported to be expressed on antigen presenting cells and various healthy nonlymphoid tissues including small intestine, ovary, testis, kidney and endothelial cells. We analyzed multiple tumor cell lines of hematopoietic and epithelial origin as well as of germ cell lineage and various gliomas by RT-PCR and FACS analysis. Both G…
Induction of accessory cell function of human alveolar macrophages by inhalation of human natural interleukin-2.
1996
Accessory function allows antigen-presenting cells to produce sufficient secondary signals for optimum T cell proliferation and interleukin-2 (IL-2) production. Alveolar macrophages are inferior accessory cells compared to monocytes (PBM). We report here that the accessory index (AI) of alveolar macrophages and PBM of patients with lung metastases of solid tumors treated with inhalations of human natural IL-2 (hnIL-2) increased following its administration (P0.005). The accessory index was significantly elevated from baseline values after 2 weeks of inhalation of 300,000 IU hnIL-2/day (8.2 +/- 10.2 compared to 1.1 +/- 1; P0.001). The inhalation of 150,000 IU also induced increases in the in…
Cloned T helper cells reverting to a resting state develop increasing sensitivity in their antigen-mediated interaction with accessory cells.
1988
A cloned murine T cell line, KIII5, specific for the polypeptide poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys [(T,G)-A--L] was compared at different stages after antigenic stimulation with respect to the conditions required for the reinduction of growth by varying concentrations of antigen presented on different types of accessory cells (AC). We show that the dose of antigen necessary for inducing half maximal proliferation in the presence of splenic AC shifts to considerably lower concentrations when the T cell blasts revert to a resting state (100 micrograms/ml on day 7 to 10 micrograms/ml on day 21-35). During the same time period the expression of interleukin 2 (IL2) receptor and the reacti…
Endothelial Nitric Oxide Synthase Regulates T Cell Receptor Signaling at the Immunological Synapse
2006
The role of nitric oxide (NO) in T cells remains controversial, and the origin and localization of endogenous NO and whether it regulates lymphocyte activation are unclear. We show here that, within minutes of binding to antigen, T cells produce NO via endothelial nitric oxide synthase (eNOS). This process required increased intracellular Ca2+ and phosphoinositide3-kinase activity. By using an eNOS-green fluorescent fusion protein and fluorescent probes to detect NO, we show that eNOS translocates with the Golgi apparatus to the immune synapse of T helper cells engaged with antigen-presenting cells (APC), where it was fully activated. Overexpression of eNOS prevented the central coalescence…
Maintenance and Function of Human CD8+ T Cells and NK Cells in Humanized Mice
2014
Human CD8+ T lymphocytes and NK cells can be successfully engrafted in highly immuno-deficient mouse strains such as NOD/shi-SCID/γgcnull (NOG), NOD/SCID/IL2Rγnull (NSG), NOD/Rag1KO/γcnull (NRG), and BALB/c-Rag2KO/γcnull (BRG) mice following reconstitution with human CD34+ hematopoietic stem cells (HSCs) or, alternatively, upon adoptive transfer of peripheral blood mononuclear cells (PBMC). These humanized immune system (HIS) mice have evolved as a promising tool to study human CD8+ T cell and NK cell-mediated immune responses to cancer and infectious diseases and to explore new approaches in adoptive immunotherapy and vaccination. However, long-term generation of CD8+ T lymphocytes and NK …
Tc9 cells, a new subset of CD8+T cells, support Th2-mediated airway inflammation
2013
Similar to T-helper (Th) cells, CD8(+) T cells also differentiate into distinct subpopulations. However, the existence of IL-9-producing CD8(+) T (Tc9) cells has not been elucidated so far. We show that murine CD8(+) T cells activated in the presence of IL-4 plus TGF-β develop into transient IL-9 producers characterized by specific IFN-γ and IL-10 expression patterns as well as by low cytotoxic function along with diminished expression of the CTL-associated transcription factors T-bet and Eomesodermin. Similarly to the CD4(+) counterpart, Tc9 cells required for their differentiation STAT6 and IRF4. Tc9 cells deficient for these master regulators displayed increased levels of Foxp3 that in t…
Strong and sustained effector function of memory- versus naïve-derived T cells upon T-cell receptor RNA transfer: Implications for cellular therapy
2012
Current protocols used to select CMV-specific T cells for adoptive immunotherapy focus on virus-specific memory T cells from seropositive donors. However, this strategy is not feasible in patients undergoing allogeneic haematopoietic stem-cell transplantation (HSCT) from CMV-seronegative donors. Here, we redirected T cells of CMV-seronegative donors with a human genetically engineered TCR recognizing an HLA-A*0201-binding peptide epitope of CMVpp65. To facilitate clinical translation of this approach, we used a non-viral expression system based on in vitro transcribed RNA and electroporation. Although memory and naive-derived T-cell subsets were both efficiently transfected by TCR-RNA, memo…