Search results for " T-Cell"

γδ T cell-based anticancer immunotherapy: Progress and possibilities

2015

Targeting components of the alternative NHEJ pathway sensitizes KRAS mutant leukemic cells to chemotherapy.

2014

Abstract Activating KRAS mutations are detected in a substantial number of hematologic malignancies. In a murine T-cell acute lymphoblastic leukemia (T-ALL) model, we previously showed that expression of oncogenic Kras induced a premalignant state accompanied with an arrest in T-cell differentiation and acquisition of somatic Notch1 mutations. These findings prompted us to investigate whether the expression of oncogenic KRAS directly affects DNA damage repair. Applying divergent, but complementary, genetic approaches, we demonstrate that the expression of KRAS mutants is associated with increased expression of DNA ligase 3α, poly(ADP-ribose) polymerase 1 (PARP1), and X-ray repair cross-comp…

Therapeutic application of T cell receptor mimic peptides or cDNA in the treatment of T cell-mediated skin diseases

2000

An 8-amino acid peptide encoding a sequence of the transmembrane region of the T cell receptor alpha chain (TCR-alpha) was shown to inhibit T cell function by preventing functional assembly of the T cell receptor (mimic peptide). To avoid systemic immunosuppression by peptide application in vivo, we used a topical application of the peptide. In the system of murine contact sensitivity, topical application of the peptide inhibited the elicitation of contact sensitivity following application of a contact allergen in sensitized animals. Alternatively, when naked DNA encoding the peptide sequence was injected into skin before application of a contact allergen to sensitized animals, local immuno…

Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis

2008

T-cell recognition of autoantigens is important in the development of autoimmune disease. Now, Hartmut Wekerle and his colleagues demonstrate that organ-specific autoimmune responses may be driven by T cells that simultaneously respond to two different autoantigens found within the same target tissue. We describe here the paradoxical development of spontaneous experimental autoimmune encephalomyelitis (EAE) in transgenic mice expressing a myelin oligodendrocyte glycoprotein (MOG)-specific T cell antigen receptor (TCR) in the absence of MOG. We report that in Mog-deficient mice (Mog−/−), the autoimmune response by transgenic T cells is redirected to a neuronal cytoskeletal self antigen, neur…

Dendritic cells, engineered to secrete a T-cell receptor mimic peptide, induce antigen-specific immunosuppression in vivo

2003

A T-cell receptor mimic peptide (TCRpep) consisting of an 8-amino-acid peptide, homologous to the transmembrane region of the T-cell receptor (TCR) alpha chain, blocks T-cell activation after systemic application. When dendritic cells (DCs) were transduced to secrete the TCRpep and injected into mice, evidence of immunosuppression was observed. In a CD8-driven allergy model, the injection of DCs transduced with the TCRpep reduced inflammation markedly and in a CD4+ T cell-dependent model of multiple sclerosis (experimental autoimmune encephalitis, EAE), injection of TCRpep-secreting DCs abrogated EAE symptoms and prolonged survival. These effects were antigen specific, because transduced DC…

Inhibition of the mixed lymphocyte reaction by T cell vaccination

1990

Immunization with attenuated activated autoreactive T cell lines and clones induces a response in syngeneic animals which can induce protection or recovery from autoimmune disease. This process has been termed T cell vaccination. The aim of the present study was to investigate the effect of immunization with MHC-reactive T cells on the mixed lymphocyte reaction (MLR). By injecting attenuated activated T cells primed for an alloantigen, we markedly reduced the MLR in both rats and mice. This depression appeared to be mediated by active suppression; lymphoid cells from T cell-vaccinated animals suppressed the MLR responsiveness of T cells from naive animals. Suppression of the MLR was not res…

Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified

2014

Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK - . Differentially expressed…

FOLLICULAR HELPER T-CELLS POPULATE THE INTRAHEPATIC INFILTRATES OF HCV GENOTYPE-1 CHRONICALLY INFECTED PATIENTS AND PREDICT THE ACHIEVEMENT OF VIROLO…

2011

Granulomatous mycosis fungoides, a rare subtype of cutaneous T-cell lymphoma

2015

Granulomatous mycosis fungoides (GMF) is an unusual histologic subtype of cutaneous T-cell lymphoma.1 The diagnosis of GMF is usually established after observation of a granulomatous inflammatory reaction associated with a malignant lymphoid infiltrate. Epidermotropism, a clue to diagnosis in classical mycosis fungoides (MF) may be absent in about 47% of cases of GMF.2 In some instances, the granulomatous component may be intense and obscures the lymphomatous component of the infiltrate.1 There are no distinctive clinical patterns associated with GMF.1, 3

A Potent Tumor-Reactive p53-Specific Single-Chain TCR without On- or Off-Target Autoimmunity In Vivo

2018

Genetic engineering of T cells with a T cell receptor (TCR) targeting tumor antigen is a promising strategy for cancer immunotherapy. Inefficient expression of the introduced TCR due to TCR mispairing may limit the efficacy and adversely affect the safety of TCR gene therapy. Here, we evaluated the safety and therapeutic efficiency of an optimized single-chain TCR (scTCR) specific for an HLA-A2.1-restricted (non-mutated) p53(264–272) peptide in adoptive T cell transfer (ACT) models using our unique transgenic mice expressing human p53 and HLA-A2.1 that closely mimic the human setting. Specifically, we showed that adoptive transfer of optimized scTCR-redirected T cells does not induce on-tar…