Search results for "T Cell"
showing 10 items of 2228 documents
The effect of the interferon-γ-inducible processing machinery on the generation of a naturally tumor-associated human cytotoxic T lymphocyte epitope …
2002
The human wild-type (wt) p53.264–272 peptide is a universal tumor antigen and recognized by HLA-A*0201 (A2.1)-restricted CTL. Generation of this epitope by constitutive 20S proteasomes is prevented by a p53 R to H hotspot mutation at the C-terminal flanking residue 273. We report on the impact of the interferon-γ (IFN-γ)-inducible proteasomal activator PA28 (11S regulator) and the immunoproteasome on the in vitro and cellular processing of wt and mutant (mut) p53 substrates. We found that production of the antigenic 264–272 peptide from wt p53 by constitutive as well as immunoproteasomes is accelerated and amplified by the PA28 activator. PA28 and (immuno)proteasomes were not capable to rec…
Targeting Acute Leukemia and Cancer by High-Affinity T-Cell-Receptor Transfer
2003
Accumulation and subsequent overexpression of human mdm2 (hdm2) and altered p53 protein is associated with high-level presentation of hdm2 and wild-type (wt) p53 derived peptides by major histocompatibility complex (MHC) class I molecules on a wide range of malignant cells. A major barrier to the design of broad-spectrum hdm2 and p53 specific immunotherapeutics for leukemia and cancer, however, has been the observation that low-level expression of hdm2 and wt p53 peptides by non-transformed tissues and cells results in self-tolerance of T-lymphocytes with high avidity for self-class I MHC / self-peptide complexes. Although the peripheral T-cell repertoire is mostly devoid of such high-avidi…
Biology and management of therapy-related acute promyelocytic leukemia.
2013
Therapy-related acute promyelocytic leukemia (t-APL) has been increasingly reported after exposure to cytotoxic and/or immunosuppressive agents given for prior malignancies or autoimmune diseases. t-APL represents both a model for better understanding human leukemogenesis and an interesting therapeutic subset which requires specific adaptations for optimal management.We discuss here potential risk factors for t-APL development and the main biologic and clinical characteristics of t-APL as compared to de-novo APL.In addition, we review therapeutic results obtained in patients with t-APL receiving conventional retinoic acid and chemotherapy and discuss new treatment opportunities with minimal…
Value of Quantitative DNA Analysis in Endocrine Tumors of the Pancreas
1997
The diagnosis of malignancy can be difficult in endocrine tumors of the pancreas. Moreover prognostically relevant factors are not available. The aim of this study was to evaluate retrospectively whether the DNA distribution pattern can differentiate between benign and malignant pancreatic endocrine tumors and secondly whether the DNA content of tumor cells gives prognostic information.Image cytometry of paraffin-embedded tumor material of 42 pancreatic endocrine tumors.In 27 benign endocrine pancreatic tumors (25 insulinomas, 2 benign nonfunctioning endocrine tumors) we could differentiate between 6 diploid, 15 hypotriploid and 6 triploid DNA histograms. In 15 malignant endocrine tumors of…
Regulatory T cell-derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway.
2014
Abstract Dendritic cells (DC) are one target for immune suppression by regulatory T cells (Treg), because their interaction results in reduced T cell stimulatory capacity and secretion of inhibitory cytokines in DC. We show that DC in the presence of Treg are more mobile as compared with cocultures with conventional CD4+ T cells and form DC–Treg aggregates within 2 h of culture. The migration of DC was specifically directed toward Treg, as Treg, but not CD4+ T cells, attracted DC in Boyden chambers. Treg deficient for the ectonucleotidase CD39 were unable to attract DC. Likewise, addition of antagonists for A2A adenosine receptors abolished the formation of DC–Treg clusters, indicating a ro…
Aminobisphosphonates as new weapons for gammadelta T Cell-based immunotherapy of cancer.
2008
BACKGROUND: Activated V gamma 9 V delta 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. OBJECTIVE: We discuss the possibility that the intentional activation of gammadelta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. METHODS: The antitumoral effects of gammadelta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. RESULTS/CONCLUSION: V gamma 9 V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic …
The transcription factor NFATc2 controls IL-6–dependent T cell activation in experimental colitis
2008
The nuclear factor of activated T cells (NFAT) family of transcription factors controls calcium signaling in T lymphocytes. In this study, we have identified a crucial regulatory role of the transcription factor NFATc2 in T cell–dependent experimental colitis. Similar to ulcerative colitis in humans, the expression of NFATc2 was up-regulated in oxazolone-induced chronic intestinal inflammation. Furthermore, NFATc2 deficiency suppressed colitis induced by oxazolone administration. This finding was associated with enhanced T cell apoptosis in the lamina propria and strikingly reduced production of IL-6, -13, and -17 by mucosal T lymphocytes. Further studies using knockout mice showed that IL-…
Endogenous CD83 Expression in CD4+ Conventional T Cells Controls Inflammatory Immune Responses
2020
Abstract The glycoprotein CD83 is known to be expressed by different immune cells including activated CD4+Foxp3+ regulatory T cells (Tregs) and CD4+Foxp3− conventional T cells. However, the physiological function of endogenous CD83 in CD4+ T cell subsets is still unclear. In this study, we have generated a new CD83flox mouse line on BALB/c background, allowing for specific ablation of CD83 in T cells upon breeding with CD4-cre mice. Tregs from CD83flox/flox/CD4-cretg/wt mice had similar suppressive activity as Tregs from CD83flox/flox/CD4-crewt/wt wild-type littermates, suggesting that endogenous CD83 expression is dispensable for the inhibitory capacity of Tregs. However, CD83-deficient CD…
Functional Analyses of Human T Cell Extravasation in a Humanized NOD/SCID/IL2Rγcnull Transplantation Model.
2009
Abstract Abstract 2448 Poster Board II-425 Donor lymphocyte graft engineering to avoid graft-versus-host (GVH) reactivity while improving graft-versus-leukemia (GVL) immunity remains of central interest in allogeneic hematopoietic stem cell transplantation (HSCT). However, appropriate models to evaluate experimental concepts of donor lymphocyte allograft engineering in vivo are missing. We, therefore, established a human-murine chimeric transplantation model using immunodeficient NOD/SCID/IL2Rγcnull (NSG) mice to evaluate GVH reactivity of human T cell grafts in vivo. Moreover, since mechanisms of immune functions resembling human GVH immunity have not yet been addressed in detail in these …
Induction of the anti-ergotypic response.
1993
The injection of syngeneic activated T cells into rodents can induce a T cell response against activation markers of the T cells, ergotopes. The responding anti-ergotypic T cells have been shown to suppress experimental autoimmune encephalomyelitis (EAE). This paper reports the characteristics of the anti-ergotypic response. It was found that irradiated activated T cells were as good as untreated living activated T cells in inducing anti-ergotypic cells in vivo. Glutardialdehyde-fixed (0.3%) cells were poor stimulators in vivo and non-stimulatory in vitro. Dilution of glutardialdehyde to 0.003% before fixation preserved the stimulatory capacity in vitro. Fixation or irradiation of T cells a…